D2R control of cocaine use

Self-administration of cocaine induces a histone acetyltransferase previously never associated with addiction, Kat5. This HAT is induced by the dopamine/acetylcholine control of striatal circuits in response to cocaine; and is absent in mice lacking the inhibitory dopamine D2 receptors from striatal cholinergic interneurons, the ChI-D2RKO mice. in the absence of Kat5 induction in ChI-D2RKO mice, these animals consume less cocaine. Furthermore,use of the Kat5 specific inhibitor eliminates the motor and sensitized response to cocaine in wild-type mice.