3.6.3.

Activation, Arousal and Psychopharmacology (2001-2002)

Activation, arousal & psychopharmacology

Course book
Course 3.6.3, Year 2001-2002
Faculty of Psychology, Maastricht University

PLANNING GROUP
Annemiek Vermeeren,
Coordinator

Faculty of Psychology, Neurocognition

UNS40 Room 4.737
Tel 388 1952
Email <a.vermeeren@psychology.unimaas.nl>

Fren Smulders

Faculty of Psychology, Experimental Psychology

UNS 40 Room 3.744
Tel 388 1909
Email: <f.smulders@psychology.unimaas.nl>

Jan Ramaekers

Faculty of Psychology, Neurocognition

UNS 40 Room 4.737
Tel 388 1951
Email <j.ramaekers@psychology.unimaas.nl>

Eric Vuurman,
Practical Coordinator

Faculty of Medicine, Neuropsychology & Psychiatry

DRT10 Room 3.013
Tel. 388 1046
Email <e.vuurman@np.unimaas.nl>

Kim Kuypers, student

Email <kkuypers@hotmail.com>

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

INDEX
Page
Title page.............................................................................................................................. 1
Planning Group.................................................................................................................... 1
Index ................................................................................................................................... 2
Schedule for 2002 ............................................................................................................... 3
Introduction........................................................................................................................... 4
Objectives............................................................................................................................. 5
Design and Procedure.......................................................................................................... 5
Lectures.......................................................................................................................... 5
Tasks............................................................................................................................... 6
Practical.......................................................................................................................... 6
Literature.............................................................................................................................. 7
Books.............................................................................................................................. 7
-General ......................................................................................................................... 7
-Arousal, activation and performance..............................................................................8
-Psychopharmacology..................................................................................................... 8
-Psychophysiology.......................................................................................................... 9
UB electronic information sources (CD-ROM).................................................................9
Journals........................................................................................................................... 9
Reader and Electronic Reader (Ereader)........................................................................10
Suggested reading per task.................................................................................................. 10
Tasks ................................................................................................................................... 15
Task 1 Bien dormir vers Benidorm ................................................................................17
Task 2 Whats new? ...................................................................................................... 18
Task 3 Data and Models that predict them: non- monotonic relations ...........................19
Task 4 Models & Data: from 1D to 3D ...........................................................................20
Task 5 Functional pathways ..........................................................................................21
Task 6 Pay attention! ..................................................................................................... 22
Task 7 Output = f(input) .................................................................................................23
Task 8 MOSA ................................................................................................................ 24
Task 9 Stress forecast ................................................................................................... 26
Task 10 Never enough .................................................................................................. 27

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

SCHEDULE for 2002

See timetable Educational Desk for exact times and rooms.
Week 1 Mo 8/4
Lecture 1 Annemiek Vermeeren opening remarks and Lecture
Sleep-wake regulation and arousal mechanisms' (ad task 1 and 2)
Eric Vuurman: Practical instructions (obligatory)
Tu 9/4
Th 11/4

Brainstorm Task 1 Bien dormir vers Benidorm

Report Task 1and brainstorm Task 2 Whats new
Practical Group 310, 311, 313 (obligatory)

Week 2

Week 3

Week 4

Mo 15/4
Tu 16/4

Lecture 2, Fren Smulders 'Models and data: an introduction' (ad task 3 and 4)
Report Task 2 and brainstorm Task 3 Data and Models that predict them

Th 18/4

Practical Group 312, 314, 315 (obligatory)

Report Task 3 and brainstorm Task 4 Models and Data: from 1D to 3D

Mo 22/4

Practical: instructions data processing and report writing (obligatory)

Tu 23/4
Th 25/4

Lecture 3 Fren Smulders, 'Models and data: the final answers?' (ad task 4)
Report Task 4 and brainstorm Task 5 Functional pathways
Report Task 5 and brainstorm Task 6 Pay attention!

Mo 29/4
Tu 30/4
Th 2/5

Day off
Queens day (Day off)
Report Task 6 and brainstorm Task 7 Output = f(input)
Practical: question time (optional)

Week 5

Mo 6/5
Tu 7/5
Th 9/5

Lecture 4 Jan Ramaekers, 'What the body does to the drug' (ad task 7)
Report Task 7 and brainstorm Task 8 MOSA and Task 9 Stress forecast
Ascension day (Day off)

Week 6

Mo 13/5

Practical: question time (optional)

Tu 14/5
Th 16/5
Fr 17/5

Lecture 5 Jan Ramaekers, 'What the drug does to the body' (ad task 8 and 9)
Task 8 and brainstorm Task 10 Never enough
Report Task 9 & 10 and course evaluation
Course examination (14:00-16:00, Sports Hall Daalhof)

Tu 21/5

Practical: deadline for handing in the report (Box outside Room 3.013 DRT 10)

We 3/7

Re-examination (11:00-13:00, UNS50 0.402)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

INTRODUCTION
Human performance is subject to considerable change and variation. For example, you may know
from own experience that your ability to concentrate varies over the day. It even varies depending on
your mood. People who are anxious or depressed perform worse on all kinds of cognitive tasks than
healthy controls. Usually your performance can improve by investing more effort. However, when the
task is long and boring your ability to concentrate seems to vanish over time anyway. Yet when
something unexpected happens you pay attention again, at least for a while.
Performance may also change due to the use of psychoactive drugs. You may be familiar with
the effects of caffeine, nicotine and alcohol. Many people drink coffee and cola or smoke and find it
helps them to concentrate. Alcohol is well known for its impairing effects on performance, especially
on car driving. Medicinal drugs penetrating the CNS such as hypnotics, anxiolytics, antidepressants,
antipsychotics, and some antihistamines can also affect cognitive and psychomotor performance.
Many drugs cause drowsiness or sleepiness, yet their mechanism of action can be very different. For
example drugs that inhibit cholinergic, noradrenergic or histaminergic neurotransmission and drugs
that enhance GABA-ergic transmission can all cause drowsiness or sleepiness. This indicates that
several neurochemical systems are involved in the regulation of sleep and waking.
When the mechanism of action of a drug is known it can be used to manipulate
neurotransmission and study the role of the neurotransmitters or receptor subtypes in cognition and
psychomotor performance. For example, stimulant drugs like amphetamine and cocaine are known to
increase speed of responses in a reaction time task, but what cognitive function or information
processing stage do they affect? Do they speed up stimulus encoding, decision making or motor
response? By manipulating task variables it is possible to deduce what stage of information
processing is affected by a drug (or any other factor that may change arousal).
Changes in performance caused by drugs, biological rhythms, emotions or environmental factors
are often explained by changes in arousal. Arousal was originally considered a unitary (or onedimensional) process underlying physiological changes and accompanying variations in alertness.
This course will make clear that this cannot be true in terms of the underlying structures, the
relationship between different physiological indices and the relationship between arousal and
performance.
The literature will refer to a wide range of psychophysiological methods and measures, such as
EEG, cardiovascular parameters, eye movements, pupil size, electrodermal measures,
electromyography and neuroendocrine assays. One of the objectives of this course is to acquire
knowledge of the way in which physiological measures are related to changes in arousal and to
discuss the limitations of the methods.
To summarize, in this course we will examine a) the effects on performance of factors influencing
arousal, such as drugs, sleep deprivation, environmental conditions and psychiatric disorders, b)
theoretical models concerned with the relation between arousal and cognitive performance, and c) the
way in which arousal is regulated in the body

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

OBJECTIVES
Acquire knowledge of:
1. Theories explaining the relation between arousal and performance
2. Task characteristics interacting with arousal and activation
3. External and internal factors affecting arousal and activation
4. Central and peripheral structures involved in the regulation of arousal and activation
5. Structure and function of neurotransmitters systems involved in arousal and activation
6. Neuropharmacological mechanisms underlying the effects of drugs on arousal and activation
7. Psychophysiological methods assessing arousal and activation

DESIGN AND PROCEDURE

This year there will be 10 tutorial group meetings, five lectures, three obligatory practical meetings
and two optional practical meetings.

Lectures
The planning group advises you to attend the lectures, since the literature for this course sometimes
requires additional explanation. Lectures are therefore intended to explain some of the more difficult
subjects, such as the cognitive-energetic model. In addition, they will provide the opportunity to ask
questions. Lecturers and topics addressed in the lectures are:
1.

Annemiek Vermeeren, opening remarks and 'Sleep-wake regulation and arousal

mechanisms' (ad tasks 1 and 2)
Eric Vuurman, Introduction to the practical (obligatory)

2.

Fren Smulders, 'Models and data: an introduction' (ad tasks 3 and 4)

3.

Fren Smulders, 'Models and data: the final answers?' (ad task 4)

4.

Jan Ramaekers, 'What the body does to a drug' (ad task 7)

5.

Jan Ramaekers, 'What a drug does to the body' (ad tasks 8 and 9)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Tasks
The rationale of the contents and order of the tasks is as follows:

Tasks 1 and 2 will introduce you to the concept of arousal in the context of sleep and
anxiety. These states are often seen as opposing ends of a continuum. The term as used in
the beginning meant generalized arousal of cortical activity (EEG), and peripheral autonomic
activity, including cardiovascular, respiratory, electrodermal and electromyographic variation. It
will be shown that the problem with the generalized construct was that the
psychophysiological indicators are usually not highly correlated within individuals and across
stimulus conditions. For these reasons the term arousal is now often used with reference to
cortical, cardiovascular or electrodermal activity.

Tasks 3 and 4 introduce a few influential models of arousal and performance. Effects of
stressors like noise and sleep deprivation on performance in easy and complex tasks will be
examined. The main objective of these tasks is to understand each model's strengths and
weaknesses in explaining existing data.

Task 5 concerns the mechanism of action of antipsychotic and stimulant drugs and their
effects on performance. The task focuses on the dopamine system.

Task 6 focuses on the specific role of noradrenaline in arousal and attention

Task 7 introduces the general concepts of pharmacokinetics or what the body does to the
drug. It intends to clarify the dose-effect relation of drugs and the time course of drug actions.

Task 8 concerns changes in activation, arousal and performance depending on the duration
and event characteristics of the task. Performance changes will be discussed in terms of
signal detection theory. In addition it will be shown that drugs from the same therapeutic class
can very different effects on arousal.

Task 9 concerns the fact that antidepressant drugs having different mechanisms of action, all
have a delayed onset of therapeutic effects. The current theory regarding the processes
underlying this delay will be explained, as well as the reasons why the side effects of
antidepressants (e.g. sedation) differ.

Task 10 concerns drug addiction. The long-term effects of addictive drugs on neural structures
and neurotransmitters systems are assumed to be an important part of the mechanism
underlying the lack of impulse control that characterizes addictive behaviors.

Practical
The practical for this course involves the conduct, analysis, and reporting of a psychological
experiment. The experiment will address the question whether cognitive performance is influenced by
noise in the environment. Each student will take a number of computerized tests and collect the data
of his/her performance. The data of all participants will be made available to each students and a

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

report about the information collected in the experiment has to be written in the form of a journal
article. Each student is expected to (individually) process the raw data, make a graphic data
presentation, and apply the relevant statistical tests. The results should be discussed within human
performance models introduced in this course. The practical consists of the following components:
1.

Introduction to the Practical (April 8). General information on the background of the research
question and instructions (including a manual) for the practical work will be given here.

2.

Data collection (April 11 or 16).

3.

Introduction to data processing (graphic presentation, SPSS) and report writing (April 22).

4.

Two interactive question times to assist you with data processing and report writing (May 2
and 13).

Please note that attendance at meetings 1, 2 and 3 is obligatory and will be checked. Question
times are not obligatory. At the start of the course (during meeting 1) a practical manual will be
distributed. Your research report should be submitted within 4 weeks after the start of data-analysis,
i.e. by Tuesday, May 21, 2002 at the latest (in the cardboard box outside Room 3.013 DRT 10).

LITERATURE
In your first year you already learned about the biopsychology of motivation, emotion and stress.
During the first week of this course it will be helpful to refresh your memory on (1) the general layout
of the (peripheral) nervous system (2) the biopsychology of emotion and stress, and (3) brain
mechanisms in sleep, using your textbooks from previous courses such as Gleitman, Kalat and Pinel.

Books
General

Kalat (2000) Biological Psychology (7th Ed). Pacific Grove CA, Brooks/Cole. (SL BF 205)

Kandel ER, Schwartz JH, Jessell TM (1995) Essentials of neural science. London, Prentice Hall
(SL WL 102)

Kandel ER, Schwartz JH, Jessell TM (2000) Principles of neuroscience. Part VII. London,
Prentice Hall (SL BF 209)

Pinel PJ (2000) Biopsychology (4th Ed). Boston, Allyn and Bacon. (SL BF 205)

Rosenzweig MR, Leiman AL, Breedlove SM (1996 and 2000) Biological Psychology. Sunderland
MA, Sinauer. (SL BF 205)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Arousal, activation and performance

Boff KR, Kaufmann L and Thomas JP (1986) Handbook of perception and human performance.
Volume II: Cognitive processes and performance. Ch 44. New York; Wiley. (SG BF 292)

Lyon, Krasnegor (1996) Attention, memory and executive function. Ch 5. Baltimore, Brooks (SL
BF 321)

Neumann O, Sanders AF (1996) Handbook of perception and action. Vol 3. Attention. Ch 7, 8.

Amsterdam, Academic Press (SG BF 292)

Parasuraman R (1998). The attentive brain. Ch 3, 10. Cambridge, MIT press. (SL BF 321)

Sanders AF (1998) Elements of human processing. Ch 9. Mahwah, Lawrence Erlbaum (SL BF

317)

Proctor RW, Van Zandt T (1994) Human factors in simple and complex systems. Allyn and Bacon
(SG TA 166)

Van Zomeren AH, Brouwer WH (1994) Clinical neuropsychology of attention. Ch 3. New York,
Oxford University Press (SL BF 321)

Wickens CD & Hollands JG (1999) Engineering psychology and human performance (3 rd Ed). Ch
2, 11, 12. Up Saddel River, Prentice Hall. (SL BF 496)

Psychopharmacology

Carvey PM (1998) Drug action in the human nervous system. Ch 2, 6. New York Oxford
University Press. (SL QV 76.5)

Feldman RS Meyer JS (1998) Principles of Neuropsychopharmacology. Ch 10. Sunderland

MA, Sinauer. (SL QV 77)

Julien RM (1998) A primer of drug action: a concise nontechnical guide to the actions, uses
and side effects of psychoactive drugs (8th Ed). New York, Freeman. (SL QV 77)

Leonard BE (1997) Fundamentals of psychopharmacology (2 nd Ed) Chichester, Wiley (SL QV

77).

Rang HP, Dale MM, Ritter JM (1999) Pharmacology (4th Ed). Edinburgh, Churchill Livingstone
(SL QV 4)

Stahl SM (1996 and 2000) Essential psychopharmacology: neuroscientific basis and practical
applications (1st and 2nd Ed). Cambridge University Press. (SL BF 207)

Psychophysiology

Andreassi JL (2000) Psychophyiology: human behavior anf physiological reponse (4 th Ed).

Mahwah, Lawrence Erlbaum (SL BF 208)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Cacioppo JT, Tassinary LG, Berntson GG (2000) Handbook of psychophysiology (2 nd Ed)

Cambridge University Press (SL BF 208)

Stern RM, Ray WJ, Quigley KS (2001) Psychophysiological recording. Oxford university
Press. (SL BF 208)

Zuckerman M (1991) Psychobiology of personality. Cambridge, Cambridge University Press.

Ch 6. (SG BF 711 / SG BF 698.9 )

UB electronic information sources (CD-ROM)

For searching journal articles on psychopharmacological subjects it is recommended to use Medline

(or the internet version PubMed), since Psychlit covers only a small part of the medical journals.

Journals

Availability of journals used in this course in the library:

UM code

electronic* Y/N

Acta Psychologica (1992..)

T 0026

Biological Psychiatry (1986..)

SV

Y: sciencedirect

Biological Psychology

T 0159

Y: sciencedirect

Br J Psychiatry

T 2720

Human Neurobiology (1983..)

T 0774

J Affect Disorders

SV

Y: sciencedirect

J Allergy Clin Immunol

T 0473

Y: (text only)

J Clin Psychiatry

--

Journal of Sleep Research

T 3385

Nature

T 0664

Neuropsychologia (1995..)

T 0668

Y: sciencedirect

Occupational and Environmental Medicine

T 1709

Y: swetsnet

Progress in Neurobiology

--

Y: sciencedirect

Psychopharmacology

T 1704

Y: swetsnet

Schizophrenia Bulletin

T 2752

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Reader & Electronic reader (Ereader)

Literature that is not available in the study landscape of the library will be provided as a reader at the
first tutorial meeting. Electronic copies (pdf files) of articles are available as an electronic reader
(Ereader). The Ereader is accessible via the homepage of the Universitys Library:
www.ub.unimaas.nl > UB&Faculties > Psychology > Students > Ereader Block 3.6.3

SUGGESTED READING PER TASK

RE = available in Reader or Ereader, SL = available at study landscape

Task 1. Bien dormir vers Benidorm

Akerstedt T (1995) Work hours, sleepiness and underlying mechanisms. J Sleep Res, 4,
Suppl,15-22. (RE, T 3385)

Borbely (1982) A two process model of sleep regulation. Human Neurobiol, 1, 195-204 (RE)

Perlis ML, Giles DE, Mendelson WB, Bootzin RR, Wyatt, JK (1997) Psychophysiological
insomnia: the behavioural model and a neurocognitive perspective. J Sleep Res, 6, 179-188.
(RE, T 3385)

Carvey PM (1998) Drug action in the Central Nervous System. Oxford University Press.
Chapter 6 Sedative-Hypnotics and Anxiolytics. Pp 123-150. (RE, SL QV 76.5)

Further reading

Horne J & Reyner L (1999) Vehicle accidents related to sleep: a review. Occup Environ Med
56 (5), 289-294. (RE, T 1709)

Lal SKJ & Craig A (2001) A critical review of the psychophysiology of driver fatigue. Biological
Psychology, 55, 173-194. (RE, T 0159)

Ziekenfondsraad (1999) Farmacotherapeutische Kompas (Dutch Pharmaceutical

Encyclopedia). Amstelveen: Ziekenfondsraad. (SL QV 55)

Video

V3108: Slapeloze nachten - Sleepless Nights. IKON (2000) 25 min. Het andere gezicht Dutch - About the biological clock, shiftwork and accidents

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Task 2 What's new

Kalat (2001) Biological Psychology (7th Ed).(SL BF 205)

Pinel PJ (2000) Biopsychology (4th Ed). Boston, Allyn and Bacon. (SL BF 205)

Rosenzweig MR, Leiman AL, Breedlove SM (2000) Biological Psychology Sunderland MA,
Sinauer. (SL BF 205)

Clow A (2001) The physiology of stress. In: Jones F, Bright J (Eds) Stress: myth, theory and
research. Harlow, Prentice Hall, Pp 47-61. (RE)

Stern RM, Ray WJ, Quigley KS (2001) Psychophysiological recording. Oxford University
Press. Ch 2. Autonomic Nervous System, Ch 5 Some basic principles of psychophysiology.
Pp 17-23, 52-69. (SLBF 208)

Further reading

Andreassi JL (2000) Psychophysiology: human behavior and physiological response (4th Ed).
Mahwah, Lawrence Erlbaum. Ch 18. Concepts in psychophysiology. (RE, SL BF 208)

Task 3 Data and models that predict them: non-monotonic relations

Andreassi JL (2000) Psychophysiology: human behavior and physiological response (4th Ed).
Mahwah, Lawrence Erlbaum. Ch 18. Activation Pp 401-405 (RE, SL BF 208)

Hockey, G. R. J. (1984). Varieties of attentional state: the effects of environment. In D. Davies

& R. Parasuraman (Eds.) Varieties of attention (pp. 449-483). New York: Academic Press.
(RE)

Hockey, G. R. J. (1986). Changes in operator efficiency as a function of environmental stress,

fatigue, and circadian rhythms. In K. R. Boff, L. Kaufman, & J. P. Thomas (Eds.), Handbook of
Perception and Human Performance. Vol 2, pp. 35-40. (RE, SG BF 292)

Task 4 Models and Data 2: from1D to 3D

Sanders AF (1998). Elements of human performance. H9: Energetics, Stress and Sustained
Attention. Pp 394-430. (SL BF 317)

Sanders AF, Wijnen JLC & Arkel van, AE (1982). An additive factor analysis of the effects of
sleep loss on reaction processes. Acta Psychologica, 51, 41-59. (RE)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Task 5 Functional pathways

Frowein HW (1981) Selective effects of barbiturate and amphetamine on information

processing and response execution. Acta Psychologica 47: 105-115 (RE)

Frowein HW, Reitsma D, Aquarius C (1981) Effects of 2 counteracting stresses on the

reaction process. In: J Long, A Baddely (eds) Attention and Performance IX, Lawrence
Erlbaum assoc, Hillsdale, New jersey, pp 574-589 (RE)

Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on
cognitive function in schizophrenia. Schizophrenia Bulletin 25: 233-255 (RE, T 2752)

Servan-Schreiber D, Bruno RM, Carter CS, Cohen JD (1998) Dopamine and the mechanisms
of cognition: part II. D-amphetamine effects in human subjects performing a selective
attention task. Biol Psychiatry 43: 723-729 (RE)

Stahl SM (1996 or 2000) Essential Psychopharmacology. Chapters 9 (psychosis and

schizophrenia), 10 (antipsychotics) 12 (drugs of abuse) (SL BF 207) Read selectively!

Task 6 Pay attention!

Clark CR, Geffen GM, Geffen LB (1989) Catecholamines and the covert orientation of
attention in humans. Neuropsychologia 27: 131-9. (RE)

Coull JT (1998) Neural correlates of attention and arousal: Insights from electrophysiology,
functional neuroimaging and psychopharmacology. Progress in Neurobiology 55 (4):343-361.
(RE)

Robbins T, Everitt B (1995) Arousal Systems and Attention. In: Gazzaniga M (ed) The
Cognitive Neurosciences. MIT Press, Cambridge MA (USA), pp 703-720. (SL QP 411)

Smith A, Nutt D (1996) Noradrenaline and attention lapses. Nature 380: 291. (RE)

Further reading

Robbins TW (1997) Arousal systems and attentional processes. Biol Psychol, 45 (1-3) 57-71
(RE)

Task 7 Output = f(input)

Carvey PM (1998) Drug Action in the Central Nervous System. Ch 2. University Press,
Oxford. pp 19-46. (SL QV 76.5)

Rosenzweig MR, Leiman AL, Breedlove SM (1996) Biological Psychology. Ch 6. Sunderland

MA, Sinauer. Pp 179-184 (SL BF 205)

Further reading

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Nutt D (1999) Alcohol and the Brain. British Journal of Psychiatry 175: 114-119. (RE)

Task 8 MOSA

Feldman RS Meyer JS & Quenzer LF (1997) Principles of neuropsychopharmacology

Chapter 10, Part IV: Histamine. Pp 445-454. Sunderland: Sinauer Associates. (SL QV 77)
Advanced reading, study according to learning objectives

Kay (2000) Effects of antihistamines on cognition and performance. J Allergy Clin Immunol
105, S622-S627 (RE, T 0473)

Lin JS (1998) The brain histaminergic system and arousal mechanisms (RE)

Sanders AF (1998). Elements of human performance. Ch 9. Energetics, stress and sustained

attention. Vigilance: Pp 430-447. (SL BF 317)

Wickens CD & Hollands JG (1999) Engineering psychology and human performance (3 rd Ed).
Ch 2. Signal detection, information theory and absolute judgement. Up Saddel River, Prentice
Hall. Pp 18-44 (SL BF 496)

Further reading

Schwartz JC, Arrang JM, Garbarg M, Traiffort, E (1995) Histamine. In: Bloom FE & Kupfer DJ
(Eds) Psychopharmacology the fourth generation of progress. New York, Raven Press. Pp
397-405. (RE, SG QV 77)

Task 9 Stress Forecast

Ressler KJ, Nemeroff CB (1999) Role of norepinephrine in the pathophysiology and treatment
of mood disorders. Biol Psychiatry 46 (9): 1219-33. (RE)

Stahl SM (1998a) Basic psychopharmacology of antidepressants, part 1: Antidepressants

have seven distinct mechanisms of action. J Clin Psychiatry 59, Suppl 4, 5-14. (RE)

Stahl SM (1998b) Mechanism of action of serotonin selective reuptake inhibitors. Serotonin

receptors and pathways mediate therapeutic effects and side effects. J Affect Disord 51 (3):
215-35. (RE)

Further reading

Stahl SM (1996, 2000) Essential Psychopharmacology. Neuroscientific Basis and Practical

Applications. University Press, Cambridge. (SL BF 207)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Task 10 Never enough

Jentsch JD, Taylor JR (1999) Impulsivity resulting from frontostriatal dysfunction in drug
abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology
146: 373-90. (RE)

Koob GF (1998) Drug Reward and Addiction. In: Zigmond MJ, Bloom FE, Landis SC, Roberts
JL, Squire LR (eds) Fundamental Neuroscience. Academic Press, San Diego, pp 1261-1277.
(SL WL 100)

Robbins TW, Everitt BJ (1999) Drug addiction: bad habits add up. Nature 398: 567-70. (RE)

Video

V2960: Verslaafd aan genot - Addicted to pleasure (1998, 6 Sep) VPRO, 25 min,
Noorderlicht- Dutch- and English with Dutch subtitles. Sequel on addiction, part 1.

V2961: Vrij van verslaving? - Free from addiction? (1998, 13 Sep) VPRO, 25 min.
Noorderlicht - Dutch- and English with Dutch subtitles. Sequel on addiction, part 2

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

Tasks

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 1. Bien dormir vers Benidorm

Jim and Janet had an argument. They were about to go on a well-earned vacation after their final
exam on Friday. Jim had suggested leaving right after the exam and drive through the night so they'll
reach the Spanish Costa as quickly as possible. No time to lose, as he has only got his father's car for
14 days. Janet argued that he would be too tired to drive, because he had studied from early morning
to late night and did not get a good night's rest all week. Jim had proposed he would sleep a couple of
hours that afternoon and then they would leave. Yet, Janet did not think that Jim would be able to
sleep during the day. His response was that he would get some sleeping pills from his mother; she
always has some flurazepam in the house. Janet was still not pleased by this plan. She had read
something about high risks for traffic accidents at night especially in the early morning. He laughed.
Things are quiet on the road at night so they can make good time! But maybe she has a point?

Jim went over to his parent's house where he ran into his mother. She asked him why he wanted
sleeping pills. After he explained his situation, she warned him not take flurazepam. It always gave her
terrible hangovers. She now uses temazepam and wakes up bright and shining.

Jim's mother has been using sleeping pills for some years now. She started having problems sleeping
when she was little over 45. It did not surprise her. Many of her friends have the same complaints:
lying in bed awake for hours, tossing and turning and worrying about family and work.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

At first her physician did not want to prescribe sleeping pills. He asked her about all her habits in
the evening, what she ate and drank, and what she did in the bedroom! He advised her to improve her
"Sleep Hygiene". However, when that did not seem to help he finally prescribed the sleeping pills she
wanted. She has tried a few times to sleep without them: when she finally falls asleep, she has terrible
dreams.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 2. What's new?

Tom, Ben and Jerry participated in a psychophysiological experiment. They were attached to several
devices measuring EEG, skin conductance, cardiovascular activity, muscle tension, eye movement
and pupil size. Blood samples were taken at fixed times through an intravenous canula in their arms.
Physiological parameters were recorded during baseline and task performance. The baseline
consisted of a period in which they just sat with their eyes closed. Subsequent tests were an auditory
attention task and a problem solving task.
Bens data could not be used for analyses, because he was disturbed during testing by something
that had upset him. The experimenter noticed that he suddenly stopped responding while his SCL,
EMG, blood pressure and heart rate suddenly strongly increased. Afterwards, out of curiosity, he
analyzed Bens blood samples. Results showed that about 20 seconds after the sudden increase in
Bens heart rate, the adrenaline levels in his blood increased by a tenfold. About 20 minutes later his
cortisol levels rose significantly.
Analysis of Tom and Jerrys data showed that:

In both subjects, at the start of the first task a) heart rate decelerated and b) EEG changed to
high frequency, low voltage activity

Physiological responses were strongest to the first stimulus and rapidly diminished thereafter

Correlations between changes in physiological parameters were low

On average, skin conductance was increased during both tasks, while heart rate was
decreased during auditory attending and increased during problem solving

The higher the heart rate and blood pressure of the subject at baseline, the smaller the
changes measured during task performance

Many of the responses above are regulated by activity in two functionally different parts of the
autonomous nervous system. All, but one, of the nerves in those systems synapse in a ganglion
before they project on their target organs. Many, but not all, organs are innervated by both systems.
The effects differ depending on the system that is most active. Heart rate is mainly regulated by the
one system, while vascular tone is mainly regulated by the other. Moreover activity in one of the
systems provokes release of a hormone from the adrenal gland, producing effects throughout the
body. Preganglionic neurons of both systems release the same neurotransmitter, while postsynaptic
neurons release different neurotransmitters.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 3. Data and Models that predict them: non-monotonic relations

The concept of 'stress' may be defined in many ways. One useful definition refers to a sub-optimal
state of arousal. The causes range from sleep loss, noise, uncomfortable high or low temperature, to
the use of medication (psychoactive drugs). The result is often (not always!) a decrement of
performance.
One of the simplest models of stress is a cumulative depletion model, as described in Hockey (1986).
According to this model, any stressor consumes extra capacity, so that a combination of stressors
usually leads to an augmenting of their effects (more depletion).
Another model predicts different results:

After a night without sleep, people perform worse than after a night of good sleep.

In a noisy environment people perform worse than in a quiet environment.

However, after a night of sleep loss noise has a positive effect on performance.

normal
sleep

Performance

Performance

0,5
sleep
deprivation

normal
sleep

0,5

sleep
deprivation

0
Quiet

Data A

Noisy

Quiet

Environment

Noisy

Environment

Data B

Below are two models of human performance. Which data does each model predict?

Modalities

Capacity to
perform task

Stages of Processing
Encoding Central Responding
Spatial
Auditory
Verbal

Model 1

Res
p

Manual

ons
e

Vocal

Model 2

Visual
Sp a
tial
Ver
Cod
bal
es

Model 3

- 20 23

Portion used to
perform task

Traditional Resource Model

3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 4. Models and Data: From 1D to 3D

I
The Yerkes-Dodson (1908) law is based on two assumptions
1. The relation between arousal and performance can be described by an inverted U.
2. The optimal level of arousal is lower for difficult tasks than for easy tasks.
Consider this: Music is OK while doing the dishes but not during a game of chess.
II
In a reaction time experiment Sanders, Wijnen, and Van Arkel (1982) varied the perceptual quality of
stimuli via degradation and the compatibility of stimulus and response. Results showed that
performance in the degraded-compatible and undegraded-incompatible conditions were differentially
affected by sleep loss (Figure 1).

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 5. Functional Pathways

Disturbances of dopaminergic neurotransmission in the brain have been implicated in the
pathophysiology of several neurological and psychiatric disorders, e.g. Parkinson disease, ADHD,
schizophrenia en mood disorders. However the mechanism through which a change in dopamine
(DA) transmission can affect human behaviour may vary.
The following are some of the most relevant findings in experimental and clinical research:

Researchers supporting the cognitive-energetic models of information processing have

repeatedly shown that amphetamines primarily activate motor processes.

Experimental studies employing a selective attention task (Eriksen Task) have shown that
amphetamines improve both motor and cognitive processes.

Dopaminergic overactivation has been associated with cognitive deficits in schizophrenic

patients

Antipsychotic drugs may induce Parkinson-like motor disturbances, i.e. extrapyramidal

symptoms (EPS), but are also claimed to improve executive cognitive function in
schizophrenic patients.

Antipsychotic drug can reduce positive symptoms in schizophrenic patients but may also
exacerbate negative symptoms

Classical antipsychotic drugs cause EPS whereas atypical antipsychotic drugs do not.

At first glance, above findings seem contradictor but fall into place when considering the functional
and regulatory roles of DA projection systems in the brain.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 6. Pay Attention!

I
Smith and Nutt (1996) administered a low dose of clonidine to subjects performing a visual reaction
time task. They predicted an increased number of "attention lapses", as reflected by longer reaction
times (> 1500 ms). This effect disappeared after administration of an alpha-2-adrenoreceptor
antagonist or when the test was conducted in a noisy environment.
II
The results below (figure 2) are from a simple reaction time experiment. Subjects had to press a
single key as quickly as possible whenever a target stimulus was presented. Stimuli appeared either
on the right or left side of a central fixation point. A visual cue was presented 1 sec before onset of the
stimulus. These could be valid (i.e. an arrow pointing to the side where the stimulus would appear),
invalid (i.e., an arrow pointing to the side opposite to where the stimulus would appear), or neutral
(i.e., an asterisk). At the beginning of each experimental session subjects were treated with placebo
or clonidine according to balanced crossover design. Results are shown in Figure 2.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 7. Output = (Input, )

...

I
The (side) effects of medicinal drugs on performance are determined by several studies. For example
studies in which:

Subjects are administered different doses of the drug

Subjects are tested at different times after drug intake (e.g. 0.5, 1.0 1,5, 3, 6, 12, 24 hours
after intake)

Subjects are treated for several weeks and tested at weekly intervals.

Subjects are elderly people

II
Subject A consumed 3 glasses of beer after fasting for at least 4 hours. Subject B consumed 4
glasses of beer in combination with a plate of chips. Their blood alcohol concentrations (BAC, in
mg/dl) were measured at 10 minute-intervals during 2.5 hours after consumption. Alcohol and food
were consumed within 30 minutes before the start of BAC measurement.

Figure 1. Blood Alcohol Concentrations (BAC, in mg/dl) over time of Subject A (triangles) and Subject B
(squares)

III
Rose: "I turn red after one glass of wine; after two I'm tipsy; after four you can carry me off."
Margaret: "I usually stop at a maximum of five glasses, beyond that I'll quickly get drunk."
Bert: "Every Saturday, I drink more than 10 beers with the people in the brass band. I just get in the
mood."

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 8. MOSA
I
Harry worked via a temporary employment agency at the MOSA factory. Well, worked? He sat in a
comfortable chair the whole day looking at tiles passing by on a conveyor belt. The only thing that he
had to do was push a button when a tile with a "visually perceptible defect" passed by. The machine
then removed the tile from the conveyor belt. Every two hours he had a 15-minute break.
The first day, however, was not easy. His boss had said that quality was very important, so Harry
did not hesitate to reject tiles with the slightest defect. To his surprise his boss was not pleased.
According to his boss, Harry not only removed all the defective tiles but also a large number of tiles
that were just fine. He should be a little bit less critical the next day.
After the second day, Harry was asked to report to his boss again. He was told he had missed a
considerable number of tiles with defects. He seemed to pay attention only for a few minutes in the
beginning of the shift and then started to make mistakes. What was the problem?
II
Sally, a colleague of Harry's, told him she nearly fell asleep during work once. She believed it had
something to do with the medication (Tavegil) she took for hay fever. It made her feel tired.
According to the package insert label, the active ingredient was clemastine. Her doctor had prescribed
it: "It's a good antihistamine, I've prescribed it for years". A yellow sticker on the box read: "This
medication may influence your reactions. Use with caution when driving a car or operating dangerous
machinery." Sally had read it but had not paid much attention to it until she had dosed off at work. She
now uses eye drops and a nose spray and never has problems.
"I have hay fever, too," said Harry, "but I bought something at the drugstore." He had the box in his
coat pocket: "Zyrtec, contains 10 mg cetirizine per tablet" was specified on the package. He did not
see a yellow sticker anywhere and had thrown the package insert label away. He also had not used
the medication during the past week. That evening, he looked up both of the medicines in the
Pharmaceutical Encyclopedia. He found Tavegil "Composition: clemastine Warning/ Caution: Use
can lead to slowed reactions and concentration problems:. One page further, he found Zyrtec. No
such warning.

[NB. Registered drugs always have a trade name and a so-called generic name. Trade
names are indicated by the and differ per country. Generic names refer to the active
ingredient and are therefore always the same. Scientific papers use generic names.]
(continued on next page)

III

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

A series of experiments registering the EEGs for animals (kittens, rabbits) across a period of 24 hours
revealed the following:
Intracerebral injection of histamine, in particular in the posterior hypothalamus, led to increased
alertness.
Injection of a specific inhibitor of the enzyme involved in the synthesis of histamine led to
decreased alertness and increased deep sleep.
Administration of a specific H1-agonist led to increased alertness and decreased deep sleep and
REM sleep. A specific H2 -agonist was not found to do this.
Administration of an H1-antagonist led to decreased alertness.
Administration of a specific H3 antagonist led to increased alertness.
The activity of histaminergic neurons displays a circadian rhythm.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 9: Stress forecast

(first some depressive episodes, but remission after treatment weeks later)
Antidepressants are wonderful drugs: they improve mood when people are sad. Isn't it surprising that
people do not use them more often? Now they use drugs such as alcohol and XTC to make them feel
better. Unfortunately, the day after using these drugs they might feel pretty bad. In contrast,
antidepressants do not cause such hangovers. Perhaps figure 1 clarifies matters.

Figure 1. Times courses of effects of antidepressant drugs.

The picture is true for tricyclic antidepressants (TCAs), specific serotonergic reuptake inhibitors
(SSRIs), specific noradrenergic reuptake inhibitors (SNRIs) and MAO inhibitors (MAOIs). Do these
classes of drugs only differ with respect to their side effects? How would the time course of side
effects look in figure 1?
Recently studies have been published suggesting that the clinical effect of SSRIs may start sooner in
patients who are simultaneously being treated with drugs that bind to 5HT autoreceptors.

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

TASK 10. Never enough

1. When I see a pack of Marlboros - you know that pattern with a white-in-red triangle - then I
have to have a cigarette. Sometimes I have that simply when I see a yield sign in traffic.
2. Felix has been homeless for years and lives on the streets. He explains how this situation
arose: "Yeah, man, all the city was my house. Drugs, huh, it was all the drugs! Yeah, ya know,
ya can't do nothing about it, ya know. It was just in my head. I didn't wanna do it anymore, but
my body just went after it, ya know. I couldn't do nothing about it, really
3. "Just leave me here in this doorway," said the junky to a passerby. "I'm trying to stop but just
heard that my best friend died of an overdose, which has got me real depressed. Just let me
sit here... I need to have a shot."
4. Every morning, they woke up fighting. They both wanted alcohol. He usually won because he
was just a little bit less addicted. So she had to get out of bed and go get the whiskey.
5. Larry complained to a fellow student that he had study really did not feel like. The fellow
student offered him a line of speed. It was his first experience with drugs. He studied for hours
on end and really enjoyed it as well.
6. "Strange," thought Larry, "this stuff makes you feel wide awake and study longer. I always
believed that people used drugs to escape from things like academic pressure"
7. In contrast to some of his old friends and what his parents feared when he was younger, Mr.
Fletcher, turned out alright. When he was a student sex, drugs, and rock 'n roll seemed more
important to him than books. Now he is head of a department in a modern IT company.
8. Mr. Fletcher had sworn off drugs totally. Yet, on rare occasions he couldn't resist the urge. To
his surprise, the drugs seemed affect him a lot faster and stronger than before.
9. One sniff was no longer enough. That was why it became such an expensive hobby.
Each of the texts relates to a concept listed below. Find the best fit:

Activation;

Reward, Reinforcement;

Dependence, addiction;

Sensitization;

Drug use or abuse versus addiction ;

Tolerance;

Impulsivity;

Withdrawal

Negative affect;

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3.6.3. Activation, Arousal and Psychopharmacology (2001-2002)

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