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  • A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2014-05-30)
Nathan J Marchant, Rana Rabei, Konstantin Kaganovsky, Daniele Caprioli, Jennifer M Bossert, Antonello Bonci, Yavin Shaham
ANOTACE

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 + GABAB receptor 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.

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Baclofen, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(±)-Baclofen, ≥98% (HPLC), solid
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Horse Serum, Donor Herd, USA origin, Heat inactivated, sterile-filtered, suitable for cell culture