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Abstract

Grant Number:	1R41DA016521-01
PI Name:	BARDO, MICHAEL T.
PI Email:	mbardo@uky.edu
PI Title:	PROFESSOR
Project Title:	Nornicotine Enantiomers and Nicotine Self Administration

Abstract: DESCRIPTION (provided by applicant): Nicotine is known to have an important role in tobacco dependence. However, in addition to nicotine, smokers are exposed to nornicotine both in the form of a tobacco alkaloid and as a metabolite that results from biotransformation of nicotine. Using an animal model of tobacco smoking in humans, we have found that nornicotine is self-administered in rats and that nornicotine pretreatment is effective in reducing nicotine self-administration. In addition, repeated administration of S(-)-nornicotine, but not R(+)-nornicotine, increases locomotor activity. In the current project, our overall hypothesis is that S(-)-nornicotine will be more potent than R(+)-nornicotine in selectively decreasing nicotine self-administration across repeated injections. The specific aims will determine if the nornicotine enantiomers differ in their ability to (1) dose dependently decrease nicotine self-administration, (2) dose-dependently decrease sucrose-reinforced responding, and (3) decrease nicotine self-administration or sucrose-reinforced responding across repeated injections. Rats will be trained to self-administer nicotine to a stable rate and then will be pretreated with varying doses of either S(-)- or R(+)-nornicotine. To determine the specificity of the decrease in nicotine self- administration, separate groups of rats will be trained to respond for sucrose reinforcement and will be pretreated with varying doses of either S(-)- or R(+)-nornicotine. In another experiment, rats will be pretreated repeatedly with either S(-)- or R(+)-nornicotine and tested for nicotine self-administration or sucrose-reinforced responding, thus assessing if effect of each nornicotine enantiomer is long-lasting or transient. The long-range goal of this preclinical work is to develop a novel medication for smoking cessation.

Thesaurus Terms:
analog, drug addiction antagonist, drug design /synthesis /production, insecticide, nicotine, pharmacokinetics, self medication, stereoisomer
smoking cessation, sucrose
behavior test, laboratory rat

Institution:	YAUPON THERAPEUTICS, INC.
	259 RADNOR CHESTER RD, STE 210
	RADNOR, PA 19087
Fiscal Year:	2003
Department:
Project Start:	01-APR-2003
Project End:	31-MAR-2004
ICD:	NATIONAL INSTITUTE ON DRUG ABUSE
IRG:	ZRG1

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