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Mu opioid receptors in the habenula : dissecting reward and aversion in addiction

Abstract : Mu opioid receptors (MORs) have been extensively studied for their addictive properties that are thought to operate through the control of reward processes. While the importance of MORs in reward is generally attributed to their presence in the mesocorticolimbic circuitry, their role in the medial habenula (MHb), the structure in which MORs are most densely expressed, remains unexplored to date. This is quite surprising given the increasing literature on the habenula’s role in addiction as well as reward/aversion processes. Here we generated a conditional knockout mouse model that lacks MORs solely in the MH band we investigated the contribution of habenular MORs in brain functions and behavioural out comes with emphasis on reward, aversion and cognition. While the performance of our mutant model did not differ in locomotor, analgesic and reward responses to morphine norincognitive tasks compared to control mice, we uncovered a novel role for MORs in aversive states.This is the first report demonstrating that MORs control both somatic and affective aversion specifically at the level of the MHb. Habenular MORs could thus be crucial to the aversive with drawal stage of addiction cycles that is thought to increase craving and prevent success in quitting.
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Submitted on : Friday, February 1, 2019 - 11:57:59 AM
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Laura-Joy Boulos. Mu opioid receptors in the habenula : dissecting reward and aversion in addiction. Biochemistry, Molecular Biology. Université de Strasbourg; McGill university (Montréal, Canada), 2017. English. ⟨NNT : 2017STRAJ123⟩. ⟨tel-02003463⟩

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