Document Detail

Extended access to nicotine self-administration leads to dependence: Circadian measures, withdrawal measures, and extinction behavior in rats.
MedLine Citation:
PMID:  17050784     Owner:  NLM     Status:  MEDLINE    
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.
Laura E O'Dell; Scott A Chen; Ron T Smith; Sheila E Specio; Robert L Balster; Neil E Paterson; Athina Markou; Eric P Zorrilla; George F Koob
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-18
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  320     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-21     Completed Date:  2007-02-12     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  180-93     Citation Subset:  IM    
Department of Molecular and Integrative Neurosciences, SP30-2400, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
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MeSH Terms
Circadian Rhythm*
Extinction, Psychological / drug effects*
Mecamylamine / pharmacology
Nicotine / administration & dosage*
Rats, Wistar
Self Administration*
Substance Withdrawal Syndrome / etiology*
Tobacco Use Disorder / etiology*
Grant Support
Reg. No./Substance:
54-11-5/Nicotine; 60-40-2/Mecamylamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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