Directly modulating the activity of the two MSN subtypes has recently provided novel insight into the molecular and functional role of D1 and D2 MSNs in addiction. We used optogenetic tools combined with a conditional (i.e., Cre-dependent) adeno-associated viral (AAV) vector expressing the blue light-activated cation channel, channelrhodopsin-2 (ChR2). We injected the vector, or a control, into the NAc of D1-Cre or D2-Cre BAC transgenic mice and then stimulated the injected region with blue light to selectively activate D1+ vs. D2+ MSNs in the context of cocaine CPP. We found that activation of D1+ MSNs potentiates induction of cocaine CPP, whereas activation of D2+ MSNs inhibits this induction (Lobo et al., 2010). As noted previously, we observed the same behavioral effects when TrkB was deleted selectively from these MSN subtypes: enhanced cocaine CPP and locomotor activity after TrkB deletion from D1+ MSNs, and reduced cocaine CPP and locomotor activity after TrkB deletion from D2+ MSNs. The likely common action of TrkB knockout and optogenetic stimulation in D2+ MSNs is their increased activity, since deletion of TrkB from these cells increases
