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Targeting the Ventral Pallidum to Treat Addictive Disorders| old_uid | 16388 |
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| title | Targeting the Ventral Pallidum to Treat Addictive Disorders |
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| start_date | 2018/10/11 |
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| schedule | 11h30 |
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| online | no |
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| details | invité par Sabrina Boulet |
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| summary | Addiction is a disorder of behavioral symptoms including sensitization to drug-associated cues, negative affect and compulsive drug seeking. Cocaine-evoked synaptic plasticity in the reward system, particularly the nucleus accumbens (NAc) and its main output structure, the ventral pallidum (VP) drives drug-adaptive behavior. However, how information is integrated downstream of the NAc remains unclear. Here, we identify the ventral pallidum (VP) as a site of convergence of direct and indirect pathways from the NAc. Cocaine potentiated output of D1-MSNs, but weakened output of D2-MSNs, occluding LTP and LTD at these synapses, respectively. Restoring basal transmission at D1-MSN-to-VP synapses abolished locomotor sensitization, whereas restoring transmission at D2-MSN-to-VP synapses normalized motivational deficits. We further identified a non-canonical population of neurons in the VP that specifically constrain reward seeking in the face of aversive consequences, which is a hallmark feature of addiction. Our results support a model by which drug-evoked synaptic plasticity in the VP mediates diverse behavioral symptoms of addiction; targeting the VP with neuromodulation may provide novel therapeutic strategies for addictive disorders. |
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| responsibles | Sadoul |
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