DOI
https://doi.org/10.25772/W895-WZ24
Defense Date
1992
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pharmacology & Toxicology
First Advisor
Thomas H. Leahey
Second Advisor
John A. Rosecrans
Abstract
Current concepts concerning nicotine's central nervous system (CNS) mechanism(s) of action suggest that this drug is producing its effects via an interaction at nicotiniccholinergic receptors (nAChRs) which open a membrane cation channel. Following initial opening of the channel, nicotine appears to induce a rapid desensitization of the nAChRs, closing the channel and resulting in a cessation of nicotine's effects. Research presented here will provide evidence of this secondary desensitization process in vivo by demonstrating nicotine's ability to induce acute tolerance in the discriminative stimulus (DS) paradigm. The ability of nicotine to elicit DS control of behavior was significantly reduced via challenge doses of (800, 1200, and 1600 ugjkg, s.c.) of nicotine administered 60-180 minutes prior to the training dose (400 ugjkg, s.c.). Eight out of twenty rats demonstrated this phenomena, with time and dose varying, suggesting that these effect may be contingent upon the individual rat studied. It appears that we have found a means of investigating cellular mechanisms in vivo using operant behavior.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-7-2015