Scientific article

Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area

Published inScience, vol. 341, no. 6153, p. 1521-1525
Publication date2013

Drug-evoked synaptic plasticity in the mesolimbic system reshapes circuit function and drives drug-adaptive behavior. Much research has focused on excitatory transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). How drug-evoked synaptic plasticity of inhibitory transmission affects circuit adaptations remains unknown. We found that medium spiny neurons expressing dopamine (DA) receptor type 1 (D1R-MSNs) of the NAc project to the VTA, strongly preferring the GABA neurons of the VTA. Repeated in vivo exposure to cocaine evoked synaptic potentiation at this synapse, occluding homosynaptic inhibitory long-term potentiation. The activity of the VTA GABA neurons was thus reduced and DA neurons were disinhibited. Cocaine-evoked potentiation of GABA release from D1R-MSNs affected drug-adaptive behavior, which identifies these neurons as a promising target for novel addiction treatments.

  • Animals
  • Cocaine/pharmacology
  • Cocaine-Related Disorders/physiopathology
  • Dopaminergic Neurons/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuronal Plasticity/drug effects
  • Synaptic Transmission/drug effects/physiology
  • Ventral Tegmental Area/metabolism
  • Gamma-Aminobutyric Acid/drug effects/metabolism
Citation (ISO format)
BOCKLISCH, Christina et al. Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. In: Science, 2013, vol. 341, n° 6153, p. 1521–1525. doi: 10.1126/science.1237059
Main files (1)
Article (Published version)
ISSN of the journal0036-8075

Technical informations

Creation12/09/2013 11:19:00 AM
First validation12/09/2013 11:19:00 AM
Update time03/14/2023 8:55:24 PM
Status update03/14/2023 8:55:24 PM
Last indexation10/18/2023 5:52:34 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack