Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum

Meaghan Creed, Niels R. Ntamati, Ramesh Chandra, Mary Kay Lobo, Christian Lüscher

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

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.

Original languageEnglish
Pages (from-to)214-226
Number of pages13
JournalNeuron
Volume92
Issue number1
DOIs
StatePublished - Oct 5 2016

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