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temporarily blinded
with a mixture of lamp black and Vase-
line applied to both eyes, failed to join a
milling school of normal fish and collided
repeatedly with them.
We do not know whether the differ-
ences between our results and those of
Parr are consequences of technique or
whether they reflect real differences be-
tween the two species; the extent of
arousal may also be important. Parr’s
fish showed panic reactions which in-
creased the more they collided, whereas
the test saithe recovered very gradually
from handling and anesthesia while
being repeatedly presented with the
school. Finally, none of our blind saithe
showed any reaction to the school within
the time scale of Parr’s experiment. It is
therefore likely that the present tech-
nique allows more chance for a blind fish
to school.
T. J. P
ITCHER
School of
and Environmental
Sciences, New University
Ulster,
Culeraine, Northern Ireland
B. L. P
ARTRIDG E
Department
Experimental
Psychology, South Parks Road,
Oxford, England
(I).
26 NOVEMBER 1976
decrease nabinuids
in severity and then
disappear after the lung-term administration
The ex-
treme sensitivity
cannabinuids suggests
that the population might serve as a model in studies
R. a T.J.P.
manuscript. New University Dawkins, This work of and was Ulster A. supported Cook research criticized in grant part the
by
to
6 May 1976; revised 8 July 1976
Cannabinoid Induced Behavioral. Convulsions in Rabbits
Abstract. A population
White rabbits has been found to exhibit
behavioral convulsions when given
New
intravenous doses
17.
15.
11.
12.
1.
2.
3.
4.
5.
6.
7.
8.
9.
Fish.
J. Behav. Scottand, these We ment ancillary Wildl. There and exact M.
thank velocity experiments of Serv. may three-dimensional 13, Agriculture facilities the for 534 be Fish. adjustment. E. Marine
the quantitative (1965).
Shaw, Bull. use is and in and Laboratory, 70, R. of progress.
H. A position S. the 197 differences Fisheries, A. full Batty gantry Baldwin, (1972).
analysis of and of the Aberdeen,
in tank saithe W.
spacing
Depart-
Anim.
of and
the
in
cited by D.
V.
R. A.
Scientific Peters H. Mills, Protasov, and Translations, Trans. T. Schooling van B. (Wiley Wijland,
M. Basov, New in for the York, Israel V. Ecology I. Program 1973);
Krumin, of Fish,
for
A.
C.
Verlag, Berlin,
Zoologica 27, 75
(1942).
E.
76, 1 (1939).
C. M. Breder, Zoologica 52, 25 (1967).
C. S. Wardle and P. D. Anthony,
Notes
M.
A.
A. Keenleyside, Behaviour 8, 183 (1955).
1, 1 (193 1).
K.
R. Hunter,
Noble and B. Curtis. Bull. Am. Mus. Nat.
Parr,
(1927); A.
References
Ecol.
49 (5)
vol. 3,
psychoactive
452.
M.
A,
as low
as 0.05 mg per kilogram of body weight
(l-3). These rabbits were subsequently
inbred and the resultant offspring were
tested with additional naturally occur-
ring and synthetic cannabinoids of mari-
juana. Here, we describe the behavioral
to 3.3 kg.
A catheter was implanted in the left ex-
ternal jugular vein so that drugs could be
administered intravenously without dis-
rupting the animal’s behavior during sub-
sequent testing. Surgery was performed
with the animals under chlorpromazine
and subsequently pentobarbital anes-
thesia. All cannabinoids except
pholino-butyrate-a”-THC (SP-11
were Nos.
or
in doses of 0.5
965
between injections of drugs to any one havioral convulsions in the rabbits when
animal. given in low doses (0.25 to 1
of cannabinoids on these rabbits. The tively similar, that is, consisting mainly
compounds
SP-111 A, of head tucks, body torsion, or front and
and
Cannabinol 15.0 3,
Cannabidiol 15.0
Cannabichromene 8.0
Gamma-morpholinobutyric
acid hydrobromide dissolved in distilled water was the vehicle for SP-1
62 63 64
Table 1. Effects of intravenous injections of cannabinoids on a population of New Zealand White
rabbits. Rabbit identification numbers are given in Fig. 1.
Ratio of
Drug
Dose
Cannabidiol 20.0
Cannabicyclol 8.0
Table 2. Development of tolerance in a strain of New Zealand White rabbits during the long-term
administration of
Asterisks indicate that no convulsion occurred; convulsions occurred
at other times of
bit
No. 1 2 3
0.5
33 0.5
0.5
34 0.5 0.5
hydrobromide
0.5
9 0.5 0.5 0.5 0.5 0.5 0.5
1 week
after
last
4 5 6 7 8 9 10
injection
3 0.5
produced convulsions
966
SCIENCE, VOL. 194
was the vehicle used for all the cannabinoids except SP- 11
acid 1.0
60
1.0
administration.
20
24
1.0 1.0 1
Dose
22
1.0
0.25 9,
0.5
0.5
1.0
on day
Identification
numbers of
rabbits tested
10
1.0 1.0
produced
rabbits
convulsed
to number
tested
0.5
0.5
The
mean latencies in seconds
standard
error) were:
a purported ac-
tive metabolite of
has been re-
ported to have a shorter onset and great-
er potency than the parent cannabinoid
(7, 8). These observations are consistent
with our findings that convulsions in-
duced by 1
have a
much shorter latency than those induced
by
111 A, and 1
11
(0.5
20.9
461.8
or
presumably because
(1.0
46.08; 11
CBN at a dose of 10
A (1 .O mg/kg) and
129.7
,001) or
of SP-11
20.02;
and
nabicyclol and cannabichromene, two
naturally occurring constituents of mari-
juana (Table 1). Cannabichromene (8.0
mg/kg) produced no convulsions or other
observable effects in either of the rabbits
tested. When cannabicyclol (8.0 mg/kg)
was given to rabbit No. 3 no convulsions
or observable change occurred. How-
ever, approximately 7 minutes after rab-
bit No. 8 had been given cannabicyclol
(8.0 mg/kg) the rabbit began to sprawl,
then went into a brief convulsive-like
thrashing, and died. A necropsy of this
rabbit showed that death was due to a
pulmonary hemorrhage which may ex-
plain this unusual finding. Finally, rabbit
Nos. 81 through 86, 89, and 90 did not
convulse with relatively high doses of
the following hallucinogens: lysergic
acid diethylamide ( 100 &kg), mescaline
(40.0
26 NOVEMBER 1976
was suf-
ficient to elicit behavioral convulsions in
four out of the five rabbits, and each of
these four rabbits became tolerant to this
higher dose. One tolerant rabbit (No. 3)
exhibited convulsions after an increase
of dosage to 2.0
and as with the
other four subjects, tolerance subse-
quently was demonstrated with this high-
er dose. Two days after becoming toler-
ant to convulsions with the highest dose,
rabbit Nos. 3 and 33 were injected with
0.5 mg of
suggesting phetamine (0.5
that
convulsions are specific to the
nabinoids.
A preliminary study in our laboratory
(2) suggested that tolerance may develop
to the convulsant inducing properties of
phencyclidine (2.0
was under-
taken. We gave five rabbits one injection
per day of 0.5
until no con-
vulsion occurred. The following and sub-
sequent days (if necessary) the dose of
(I
and 20
psilocybin (3.0
.O
and
Tucson 85721
M
ARTIN
P
AUL
11
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Dalzell, H.
Dalzell, J. Sheehan, H. Pars, Science 177, 442
(1972).
L. Lemberger, J. Axelrod, I. Kopin, Pharmacol.
Rev. 23,371 (1971).
L. Lemberger and A.
29,825 (1973).
B. Zitko, J. Howes, R.
31,365 (1973).
R. Karler, W. Cely, S. Turkanis, Life Sci. 13,
1527 (1973).
S. Turkanis, W. Cely, D. Olsen, R. Karler, Res.
Commun. Chem. Pathol. Pharmacol. 8, 231
(1974).
This research was supported by grant 9 ROl-DA
01448 from the National Institute of Drug Abuse
(NIDA) of the Alcohol, Drug Abuse and Mental
Health Administration. We thank M. Braude of
the NIDA for the supply of cannabinoids and for
her encouragement, and H. Pars of Sharps
Associates for providing SP- 11
61,
107 (1970).
L. E. Hollister,
P.
p. 363.
P. F.
Sci., in press.
W. Hohenboken and G. Nellhaus, J.
B. C. Jones, L. Chin,
V. Longo,
and