RATIONALE: Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced-nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood. OBJECTIVE: The objective of this study was to examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. METHODS: Rats were trained for ICSS and NSA (0.06 mg/kg per infusion). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg per infusion were examined. Following reacquisition of NSA (0.06 mg/kg per infusion), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. RESULTS: Reducing the NSA unit dose produced partial compensation as indicated by the increased infusion rates, but a 35% mean decrease in daily nicotine intake. The magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine seeking during extinction. CONCLUSIONS: Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine seeking during early abstinence.
RATIONALE: Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced-nicotinetobacco products. Factors contributing to individual variability in compensation are poorly understood. OBJECTIVE: The objective of this study was to examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. METHODS:Rats were trained for ICSS and NSA (0.06 mg/kg per infusion). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg per infusion were examined. Following reacquisition of NSA (0.06 mg/kg per infusion), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. RESULTS: Reducing the NSA unit dose produced partial compensation as indicated by the increased infusion rates, but a 35% mean decrease in daily nicotine intake. The magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine seeking during extinction. CONCLUSIONS: Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine seeking during early abstinence.
Authors: Mark G LeSage; Dan E Keyler; Don Shoeman; Donna Raphael; Gregory Collins; Paul R Pentel Journal: Pharmacol Biochem Behav Date: 2002-05 Impact factor: 3.533
Authors: Saul Shiffman; Joe G Gitchell; Kenneth E Warner; John Slade; Jack E Henningfield; John M Pinney Journal: Nicotine Tob Res Date: 2002 Impact factor: 4.244
Authors: Matthew T Weaver; Maggie Sweitzer; Sarah Coddington; Jaimee Sheppard; Nicole Verdecchia; Anthony R Caggiula; Alan F Sved; Eric C Donny Journal: Nicotine Tob Res Date: 2012-01-04 Impact factor: 4.244
Authors: Andrew C Harris; Laura Tally; Clare E Schmidt; Peter Muelken; Irina Stepanov; Subhrakanti Saha; Rachel Isaksson Vogel; Mark G LeSage Journal: Drug Alcohol Depend Date: 2014-12-23 Impact factor: 4.492
Authors: M G LeSage; M Staley; P Muelken; J R Smethells; I Stepanov; R I Vogel; P R Pentel; A C Harris Journal: Drug Alcohol Depend Date: 2016-09-01 Impact factor: 4.492