Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum.
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.
Department of Basic Neurosciences, University of Geneva, Rue Michel-Servet 1, 1205 Geneva, Switzerland.
Meaghan
M
Creed
Department of Basic Neurosciences, University of Geneva, Rue Michel-Servet 1, 1205 Geneva, Switzerland.
Niels R
NR
Ntamati
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
Ramesh
R
Chandra
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
Mary Kay
MK
Lobo
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.
Christian
C
Lüscher
D000818:Animals; D066187:Basal Forebrain / Q000187:drug effects* / Q000502:physiology*; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D012054:Reinforcement, Psychology
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine
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