Effects of opioid receptor blockade on the renewal of alcohol seeking induced by context: relationship to c-fos mRNA expression

Authors

  • Peter W. Marinelli,

    1. Neurobiology of Alcohol Section, Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada
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  • Douglas Funk,

    1. Neurobiology of Alcohol Section, Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada
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  • Walter Juzytsch,

    1. Neurobiology of Alcohol Section, Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada
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  • Zhaoxia Li,

    1. Neurobiology of Alcohol Section, Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada
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  • A. D. Lê

    1. Neurobiology of Alcohol Section, Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada
    2. Departments of Pharmacology and Psychiatry, University of Toronto, Toronto, Ontario, Canada
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Dr Peter Marinelli, as above.
E-mail: Peter_marinelli@camh.net

Abstract

Contextual stimuli associated with alcohol availability can induce alcohol seeking during abstinence. Using a renewal procedure, we tested the effect of opioid receptor blockade on context-induced alcohol seeking, and its relationship to the activity of brain sites involved in learning and reward. Thirty-six male Wistar rats were trained to lever press for a 12% (w/v) alcohol solution before undergoing extinction sessions (no alcohol delivery). Half of the rats underwent training, extinction and testing in a single context with a distinct set of olfactory, visual, auditory and tactile properties [training, extinction and test in Context A (AAA)]. The other half were trained and extinguished in different contexts and returned to the training context on the test day [training, extinction and test in Contexts A, B and A, respectively (ABA)]. On the test day, the rats from each condition were pre-treated with either saline or 1 mg/kg naltrexone (s.c.) and tested for alcohol seeking. Immediately following the test session, rats were killed and their brains were analysed for c-fos mRNA expression using in-situ hybridization. Re-exposure to the alcohol-associated context (ABA) significantly increased operant behaviour on the previously active lever relative to the AAA groups and this increased responding was associated with increased c-fos mRNA expression in the basal and lateral amygdala and the CA3 subregion of the hippocampus. Naltrexone pre-treatment attenuated context-induced alcohol seeking and inhibited c-fos mRNA expression in the lateral amygdala and CA3. Our findings point to a critical role for the basolateral amygdala and dorsal hippocampus in mediating context-induced renewal of alcohol seeking and suggest that opioidergic mechanisms mediate this effect.

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