Abstract
The present study characterized nicotine intake, circadian patterns of food and water intake, precipitated somatic signs of withdrawal, and extinction of nicotine-seeking behavior in rats with 23-h access to intravenous self-administration (IVSA). Separate groups of animals were allowed access to nicotine IVSA (0.015, n = 9; 0.03, n = 14; 0.06, n = 16; mg/kg/0.1 ml infusion/s; fixed ratio 1) and trained to nosepoke for food and water 23 h/day for 40 consecutive days. Somatic signs of nicotine withdrawal were examined following saline or mecamylamine administration (1.5 mg/kg i.p.), and extinction of nicotine-seeking behavior was assessed. A dose-dependent decrease in lever responding and an increase in nicotine intake were observed, with the highest nicotine dose producing the lowest amount of lever responding and the highest amount of nicotine intake. Nicotine acutely reduced diurnal and nocturnal food intake, producing smaller and fewer meals, and an increased rate of eating. Differences in rate of nicotine intake between the light and dark phase decreased significantly, especially in rats receiving higher unit nicotine doses (0.03 and 0.06 mg/kg), along with long-term decreases in the circadian profile and amplitude of feeding. Mecamylamine precipitated robust withdrawal signs, the magnitude of which was positively correlated with the total amount of self-administered nicotine. Extinction of nicotine-seeking behavior was observed and was facilitated by removal of nicotine-associated cues. The results demonstrate that rats will self-administer nicotine to the point of producing dependence, as measured by somatic signs, resistance to extinction, and measures of food intake.
Footnotes
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This research was supported by the Robert Wood Johnson Foundation Tobacco Etiology Research Network and the Tobacco-Related Disease Research Program (TRDRP) of the State of California (Grant 12RT-0099 to G.F.K. and Grant 15RT-0022 to A.M.). N.E.P. was supported by an Individual Postdoctoral Fellowship 14-FT0056 from the TRDRP. E.P.Z. was supported by Grant DK64871 from the National Institute of Diabetes and Digestive and Kidney Diseases. This is publication number 17959-MIND from The Scripps Research Institute.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.105270.
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ABBREVIATIONS: IVSA, intravenous self-administration; MESOR, midline estimating statistic of rhythm; ANOVA, analysis of variance.
- Received March 26, 2006.
- Accepted October 17, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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