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Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum

Chandra, Ramesh
Lobo, Mary Kay
Published in Neuron. 2016, vol. 92, no. 1, p. 214-226
Abstract Addiction is a disorder of behavioral symptoms including enhanced incentive salience of drug-associated cues, but also a negative affective state. Cocaine-evoked synaptic plasticity in the reward system, particularly the nucleus accumbens (NAc), 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 medium spiny neurons expressing dopamine (DA) receptor type 1 (D1-MSNs) and type 2 (D2-MSNs) of the NAc. Repeated in vivo cocaine exposure potentiated output of D1-MSNs, but weakened output of D2-MSNs, occluding LTP and LTD at these synapses, respectively. Selectively restoring basal transmission at D1-MSN-to-VP synapses abolished locomotor sensitization, whereas restoring transmission at D2-MSN-to-VP synapses normalized motivational deficits. Our results support a model by which drug-evoked synaptic plasticity in the VP mediates opposing behavioral symptoms; targeting the VP may provide novel therapeutic strategies for addictive disorders.
PMID: 27667004
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Research group Mécanismes cellulaires de la dépendance et de l'addiction (520)
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CREED, Meaghan et al. Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum. In: Neuron, 2016, vol. 92, n° 1, p. 214-226. doi: 10.1016/j.neuron.2016.09.001 https://archive-ouverte.unige.ch/unige:89206

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Deposited on : 2016-11-21

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