Effect of optogenetic manipulation of accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine‐induced behavioral sensitization

Repetitive exposure to addictive drugs causes synaptic modification in the mesocorticolimbic dopamine ( DA ) system. Dopamine D1 receptors (D1R) or D2 receptors (D2R) expressed in the medium spiny neurons ( MSN s) of the nucleus accumbens ( NA c) play critical roles in the control of addictive behaviors. Optogenetic activation of D2R‐expressing MSN s (D2R‐ MSN s) in the NA c previously demonstrated that these neurons play a key role in withdrawal‐induced plasticity. Here, we examined the effect of optogenetic inhibition of D2R‐ MSN s in the NA c on cocaine‐induced behavioral sensitization. Adeno‐associated viral vectors encoding archaerhodopsin (ArchT) were delivered into the NA c of D2‐Cre transgenic mice. Activation of ArchT produced photoinhibition of D2R‐ MSN s and caused disinhibition of neighboring MSN s in the NA c. However, such optogenetic silencing of D2R‐ MSN s in the NA c in vivo affected neither the initiation nor the expression of cocaine‐induced behavioral sensitization. Similarly, photoinhibition of NA c D2R‐ MSN s in the NA c during the drug withdrawal period did not affect the expression of cocaine‐induced behavioral sensitization. More detailed analysis of the effects of optogenetic activation of D2R‐ MSN s suggests that D2R‐ MSN s in the NA c exert important modulatory effects on neighboring MSN neurons, which may control the balanced output of NA c MSN s to control addictive behaviors.