title: Exposure to cocaine regulates inhibitory synaptic transmission from the ventral tegmental area to the nucleus accumbens.
abstract: Synaptic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) make up the backbone of the brain reward pathway, a neural circuit that mediates behavioural responses elicited by natural rewards as well as by cocaine and other drugs of abuse. In addition to the well-known modulatory dopaminergic projection, the VTA also provides fast excitatory and inhibitory synaptic input to the NAc, directly regulating NAc medium spiny neurons (MSNs). However, the cellular nature of VTA-to-NAc fast synaptic transmission and its roles in drug-induced adaptations are not well understood. Using viral-mediated in vivo expression of channelrhodopsin 2, the present study dissected fast excitatory and inhibitory synaptic transmission from the VTA to NAc MSNs in rats. Our results suggest that, following repeated exposure to cocaine (15 mg kg(-1) day(-1) × 5 days, i.p., 1 or 21 day withdrawal), a presynaptic enhancement of excitatory transmission and suppression of inhibitory transmission occurred at different withdrawal time points at VTA-to-NAc core synapses. In contrast, no postsynaptic alterations were detected at either type of synapse. These results suggest that changes in VTA-to-NAc fast excitatory and inhibitory synaptic transmissions may contribute to cocaine-induced alteration of the brain reward circuitry.
authors.affiliation: Y. Dong, Y. Huang: University of Pittsburgh, 210 Langley Hall, Department of Neuroscience, PA 15260, USA. yandong@pitt.edu; huangy3@upmc.edu.
authors.forename: Masago
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Mami
authors.initials: M
authors.lastname: Otaka
authors.forename: Peter A
authors.initials: PA
authors.lastname: Neumann
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Wang
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D062308:Optogenetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D003042:Cocaine
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