Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum.
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Creed M
Department of Basic Neurosciences, University of Geneva, Rue Michel-Servet 1, 1205 Geneva, Switzerland.
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Ntamati NR
Department of Basic Neurosciences, University of Geneva, Rue Michel-Servet 1, 1205 Geneva, Switzerland.
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Chandra R
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
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Lobo MK
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
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Lüscher C
Department of Basic Neurosciences, University of Geneva, Rue Michel-Servet 1, 1205 Geneva, Switzerland; Service de Neurologie, Department of Clinical Neurosciences, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland. Electronic address: christian.luscher@unige.ch.
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English
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.
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Language
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Open access status
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bronze
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Persistent URL
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https://sonar.ch/global/documents/116686
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