Acquisition, Extinction, Recovery, and Reversal of Different Response Sequences Under Conditional Control by Nicotine in Rats

ABSTRACT

Complex voluntary behaviors occur in sequence. Eight rats were trained in an operant procedure that used nicotine and non-drug (saline) states as interoceptive cues that signaled which of two behavioral sequences led to food reward. The distal and proximal responses in the chain were always maintained on variable interval 30-sec and fixed ratio-1 schedules, respectively, and rate differences between the responses were used as the dependent variable. Extinction and reversal training was conducted. Distal response rates were significantly greater than proximal response rates during training, testing, extinction, and reversal learning. These data suggest that (a) nicotine can establish interoceptive control over different response sequences, and (b) extinction of one response sequence may be state-dependent. The clinical relevance of extinction of complex behavioral repertoires such as drug-seeking and drug-taking behavior that are evoked by specific interoceptive cues is addressed in regard to drug abuse treatment and relapse.

Keywords:

• drug discrimination
• drug-seeking behavior
• extinction
• heterogeneous chain
• nicotine
• rats
• relapse

Acknowledgments

This work was supported by New Hampshire IDeA Network of Biological Research Excellence (NH-INBRE) NIH Grant Number 1P20RR030360-01 from the INBRE Program of the National Center for Research Resources. I am indebted to Drs. Torbjörn (Toby) U. C. Järbe of the Center for Drug Discovery at Northeastern University, Boston, MA, Ian P. Stolerman of the Institute of Psychiatry, King's College, London, England, and Leigh Panlillio of NIDA for reading and commenting various versions of this article. Special thanks go to Lauren Morse & Erin Bryant for data collection and data entry, and Dustin MacConnel & Donna Pioli for their diligent animal husbandry.