1. A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence
- Author
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Konstantin Kaganovsky, Antonello Bonci, Nathan J. Marchant, Jennifer M. Bossert, Daniele Caprioli, Rana Rabei, Yavin Shaham, Anatomy and neurosciences, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention
- Subjects
Male ,medicine.medical_specialty ,Reinforcement Schedule ,Alcohol Drinking ,Lateral hypothalamus ,media_common.quotation_subject ,Self Administration ,Context (language use) ,Nucleus accumbens ,chemistry.chemical_compound ,Punishment ,Recurrence ,Internal medicine ,medicine ,Animals ,media_common ,Alcohol Abstinence ,General Neuroscience ,Articles ,Abstinence ,Rats ,Behavior, Addictive ,Baclofen ,Endocrinology ,chemistry ,Muscimol ,Hypothalamic Area, Lateral ,Anesthesia ,Alcohol ,Context ,Relapse ,Neuroscience (all) ,Psychology ,Self-administration - Abstract
In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA+ GABABreceptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse.
- Published
- 2014