D2R striatopallidal neurons inhibit both locomotor and drug reward processes

The striatum contains two distinct types of GABAergic neurons, striatonigral and striatopallidal cells. Durieux and colleagues genetically ablated the striatopallidal population in mice, uncovering specific roles for these neurons in the control of locomotion and the response to the addictive drug amphetamine. The specific functions of dopamine D 2 receptor–positive (D 2 R) striatopallidal neurons remain poorly understood. Using a genetic mouse model, we found that ablation of D 2 R neurons in the entire striatum induced hyperlocomotion, whereas ablation in the ventral striatum increased amphetamine conditioned place preference. Thus D 2 R striatopallidal neurons limit both locomotion and, unexpectedly, drug reinforcement.