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The Journal of Neuroscience, February 8, 2006, 26(6):1872-1879; doi:10.1523/JNEUROSCI.4895-05.2006

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Behavioral/Systems/Cognitive
Increased Vulnerability to Nicotine Self-Administration and Relapse in Alcohol-Naive Offspring of Rats Selectively Bred for High Alcohol Intake

A. D. Lê,^1,2,3 Z. Li,¹ D. Funk,¹ M. Shram,^1,2 T. K. Li,⁴ and Y. Shaham⁵

¹Department of Neuroscience, Center for Addiction and Mental Health, Toronto, Ontario, Canada M5S 2S1, Departments of ²Pharmacology and ³Psychiatry, University of Toronto, Toronto, Ontario, Canada M5S 1A8, ⁴Office of the Director, National Institute on Alcohol Abuse and Alcoholism–National Institutes of Health (NIH)–Department of Health and Human Services, Bethesda, Maryland 20892, and ⁵Behavioral Neuroscience Branch, Intramural Research Program–National Institute on Drug Abuse–NIH–Department of Health and Human Services, Baltimore, Maryland 21224

Correspondence should be addressed to Dr. A. D. Lê, Department of Neurosciences, Center for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada M5S 2S1. Email: anh_le{at}camh.net

The prevalence of smoking in human alcoholics is substantially higher than in the general population, and results from twin studies suggest that a shared genetic vulnerability underlies alcohol and nicotine addiction. Here, we directly tested this hypothesis by examining nicotine-taking behavior in alcohol-naive offspring of alcohol-preferring (P) rats and alcohol-nonpreferring (NP) rats that had been selectively bred for high and low alcohol intake. The self-administration of intravenous nicotine (0.015–0.060 mg/kg per infusion) in P rats was more than twice than that of NP rats. Nicotine seeking induced by reexposure to nicotine cues in extinction tests was also substantially greater in P rats than in NP rats. In a subsequent relapse test, priming nicotine injections reinstated drug seeking in P rats but not NP rats. P rats also self-administered higher amounts of oral sucrose (1–20%) than NP rats, a finding consistent with previous reports. In contrast, self-administration of intravenous cocaine (0.1875–1.125 mg/kg per infusion) was remarkably similar in the P and NP rats; however, P–NP differences in cocaine seeking emerged in subsequent extinction and cocaine priming-induced reinstatement tests. In both cases, lever responding was higher in P rats than in NP rats. Thus, alcohol-naive offspring of rats genetically selected for high alcohol intake are highly susceptible to nicotine self-administration and relapse, and this susceptibility is not likely caused by general reward deficits in NP rats. The present findings provide experimental evidence for the hypothesis that a shared genetic determinant accounts for the co-abuse of nicotine and alcohol.

Key words: extinction; genetic vulnerability; nicotine self-administration; P rats; NP rats; reinstatement; relapse

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Received May 31, 2005; revised Dec. 18, 2005; accepted Dec. 19, 2005.

Correspondence should be addressed to Dr. A. D. Lê, Department of Neurosciences, Center for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada M5S 2S1. Email: anh_le{at}camh.net

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