Frontiers in Behavioral Neuroscience (Oct 2014)
Optogenetics reveals a role for accumbal medium spiny neurons expressingdopamine D2 receptors in cocaine-induced behavioral sensitization
Abstract
Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have beenproposed to contribute to drug-mediated addictive behaviors. Here we have used anoptogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressingdopamine D2 receptors (D2R) in cocaine-induced behavioral sensitization. Adeno-associatedviral vectors coding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cretransgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2RMSNsform local inhibitory circuits, because photostimulation of D2R-MSN evokedinhibitory postsynaptic currents in neighboring MSNs. Photostimulation of NAc D2R-MSNin vivo affected neither the initiation nor the expression of cocaine-induced behavioralsensitization. However, photostimulation during the drug withdrawal period attenuatedexpression of cocaine-induced behavioral sensitization. These results show that D2R-MSNsof NAc play a key role in withdrawal-induced plasticity and may contribute to relapse aftercessation of drug abuse.
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