Nicotinic receptors and Parkinson's disease Institution: Investigator(s): Award Cycle: Subject Area: Award Type: Abstracts Initial

Award Abstract The Parkinson's Institute Maryka Quik , Ph.D. 2002 (Cycle 11) Nicotine Dependence Research Project Awards Grant #: 11RT-0216 Award: $752,940

Although tobacco use is generally associated with detrimental health related effects including respiratory disease, cardiovascular disease and cancer, the large series of studies done between 1961 and 2000 show that there is about a 50% decrease in the incidence of Parkinsons disease in tobacco users. P disease is a relatively common movement disorder which occurs in approximately 1% of the population over 50 years of age and is due to degeneration o nerve cells in the brain. Treatments available to date involve administration of the dopamine drug L-dopa and/or other drugs which stimulate the dopamin brain. Although quite beneficial in the early stages of the disease, these drugs become less effective with continued treatment. Disease progression is ine immobility and dementia present at the end stages. The development of new approaches is thus essential for Parkinsons disease management. Our ratio investigating a role for nicotine stems from recent studies which show that nicotine drug therapy, in combination with l-dopa, may be beneficial in relieving motor and memory difficulties that occur after nigrostriatal degeneration, and furthermore from experimental evidence which shows that nicotine may exer protection against nerve cell damage. The goal of our research is to study nicotinic receptors in brain tissue in an animal model of Parkinsons disease. Nicotinic receptors are the molecules in are activated by nicotine. Experimental studies have shown that nicotinic receptors are decreased in some brain areas in Parkinsons disease. The fact th decreased in this neurological disorder could suggest that stimulation of the receptors which remain may result in a return of functions somewhat closer to However, when nicotine enters the body either through smoking, or use of the nicotine patch or gum, it stimulates many different types of nicotinic recepto brain and in the rest of the body. Nicotine treatment may therefore result in numerous biological effects in the body, only some of which are desirable or b this reason it is important to identify which nicotinic receptors are changed in Parkinsons disease. Once this is known, it may be possible to develop drug the receptors that are deficient in Parkinsons disease, and thus optimize beneficial and minimize negative side effects. To study the receptors that are ch Parkinsons disease brain, we will use a number of different experimental techniques and approaches involving drugs and reagents which target nicotinic different ways. This work may lead to the development of new therapies for the treatment of Parkinsons disease.

Publications Declines in different beta-2* containing nicotinic receptor populations in monkey striatum after nigrostriatal damage. Periodical: Journal of Pharmacology and Experimental Therapeutics Index Medicus: Authors: Kulak JM, Musachio JL, McIntosh JM, Quik M Yr: 2002 Vol: 303 Nbr: Array Abs: Differential declines in striatal nicotinic receptor subtype function after nigrostriatal damage in mice. Periodical: Molecular Pharmacology Index Medicus: Authors: Quik M, Sum JD, Whiteaker P, McCallum SE, Marks MJ, Musachio JM, McIntosh JM, et al. Yr: 2003 Vol: 63 Nbr: Abs: L-Dopa treatment modulates nicotinic receptors in monkey striatum. Periodical: Molecular Pharmacology

ART Pg: 633-639

ART Pg: 1169-1179