Although nicotine is the major drug of abuse, little information is available on its sites and mechanism of action in the central nervous system. The proposed research is aimed at an understanding of the biochemical and pharmacologic parameters of the nicotine recognition site in rat brain as well its neuroanatomical distribution and functional significance.
The specific aims are 1) to isolate and purify the nicotine recognition sites by affinity chromatography; 2) to examine their biochemical requirements and structure-activity relations employing a variety of nicotine analogues; 3) to prepare monoclonal antibodies to the purified binding sites; 4) to investigate the neuroanatomical localization of the nicotine recognition sites using immunocytochemical and autoradiographic techniques. A 3H-labeled affinity ligand will be used for in vivo labeling of the binding sites. Chronic binding and behavioral studies will be performed utilizing nicotine and mecamylamine, a nicotine antagonist. Nicotine analogues and related drugs will also be screened for their ability to antagonize the actions of nicotine in the brain. The studies may provide insight into the molecular mechanisms and sites of action of nicotine in the brain; and they may provide a therapeutic basis for dealing with the problem of tobacco smoking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA000464-14
Application #
3206763
Study Section
(DABB)
Project Start
1973-06-01
Project End
1990-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
14
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627