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

Authors:
  • ZLZ. Li
    Z. Li
  • DFD. Funk
    D. Funk
  • MSM. Shram
    M. Shram
  • TLT. K. Li
    T. K. Li
  • YSY. Shaham
    Y. Shaham
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Abstract
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.

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