Although numerous studies have examined the motivational effects of nicotine withdrawal using intracranial self-stimulation (ICSS) threshold assays, relatively few have employed other methods for assessing motivation that use naturally reinforcing stimuli (e.g., food). The objective of the present study was to determine the effects of nicotine withdrawal on motivation using a progressive-ratio (PR) schedule of sucrose pellet delivery. Rats were trained to respond for sucrose pellets under a PR schedule. When stable breaking points and response rates were achieved, PR sessions were suspended and rats were exposed to a continuous infusion of saline or nicotine (3.2 or 8.0 mg/kg/day of the base) via subcutaneous osmotic minipump for nine days. On day nine, pumps were removed. PR sessions resumed 22 h later and continued daily for five consecutive days. Only rats exposed to 8.0 mg/kg/day nicotine exhibited a significant decrease in breaking point and overall response rate compared to saline-exposed rats on day one of nicotine withdrawal. These rats also showed an increasing trend in breaking point and overall response rate over the course of withdrawal, such that these measures were significantly increased on day five of withdrawal compared to baseline. Response rates under each ratio in the PR progression in rats exposed to 8.0 mg/kg/day did not differ from baseline or from those in saline-treated rats, suggesting suppression of breaking points and overall response rates were not attributable to nonspecific motor impairment. In addition, changes in performance throughout the protocol were not associated with changes in body weight. Consistent with findings from ICSS studies, the present study demonstrates that nicotine withdrawal can produce a motivational deficit as indexed under a PR schedule. However, in contrast to ICSS, PR performance appears to be sensitive to increases in motivation late in the withdrawal period. Therefore, PR schedules of natural reinforcement may provide information on the motivational effects of nicotine withdrawal complimentary to that obtained from ICSS threshold studies.
Bibliographical noteFunding Information:
The authors thank Sarah Polcher and Jason Ross for their technical assistance in completing this study. The authors also appreciate the helpful comments provided by Jason Ross and Andrew Harris on earlier versions of the manuscript. These data were presented at the 67th Annual Meeting of the College on Problems of Drug Dependence, June 2005, Orlando, FL. Supported by NIDA/NCI grant P50-DA 013333.
- Progressive-ratio schedule