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Targeting the Ventral Pallidum to Treat Addictive Disorders

le 11 octobre 2018

Séminaire de Meaghan Creed (University of Maryland School of Medicine, Baltimore, USA)

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.

Meaghan Creed est invitée par Sabrina Boulet.

Infos pratiques


Amphi Serge Kampf
Mise à jour le 6 septembre 2018

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