Effects of opioid receptor blockade on the renewal of alcohol seeking induced by context: relationship to c-fos mRNA expression.
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.
Marinelli
Peter W
PW
Neurobiology of Alcohol Section, Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, University of Toronto, Ontario, M5S 2S1, Canada. Peter_marinelli@camh.net
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Douglas
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Juzytsch
Walter
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Zhaoxia
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D019973:Alcohol-Related Disorders / Q000209:etiology / Q000523:psychology*; D000438:Alcohols / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010812:Physical Stimulation / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*; D012646:Self Administration / Q000379:methods
D000438:Alcohols; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011957:Receptors, Opioid; D009271:Naltrexone