Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have 
been proposed to contribute to drug-mediated addictive behaviors. Here we have 
used an optogenetic approach to examine the role of NAc medium spiny neurons 
(MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral 
sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) 
were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to 
selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory 
circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic 
currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo 
affected neither the initiation nor the expression of cocaine-induced behavioral 
sensitization. However, photostimulation during the drug withdrawal period 
attenuated expression of cocaine-induced behavioral sensitization. These results 
show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and 
may contribute to relapse after cessation of drug abuse.