Habitual drug-seeking behavior is essential in the transition from recreational drug use to compulsive drug use and is regulated by the dopamine (DA) system of the dorsal striatum (DS). However, a comparative study of the two subtypes of DA receptors, D1 receptors (D1R) and D2 receptors (D2R), which have opposite regulatory functions, in habitual drug-seeking behavior is absent. Moreover, the effects of L-type calcium channels (LTCCs) and the subtypes Ca(v)1.2 and Ca(v)1.3, which are downstream of D1R and D2R, respectively, on habitual drug-seeking behavior have yet to be revealed. Therefore, based on the establishment of habitual cocaine-seeking behavior with changeable fixed interval (FI) self-administration (SA) training in rats, we compared the distinctive changes in D1R vs. D2R and Ca(v)1.2 vs. Ca(v)1.3 in the expression of habitual cocaine-seeking behavior in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). Our results showed that approximately forty percent of the animals exhibited habitual behavior after cocaine SA training. In addition, the total and membrane Ca(v)1.2 and D1R in the DLS demonstrated higher expression, but the total and membrane Ca(v)1.3 and D2R in the DMS demonstrated lower expression in well-established cocaine habitual behavior animals compared with non-established habitual behavior animals. These results suggested that upregulation of D1R-Ca(v)1.2 signaling may enhance the function of the DLS and that inactivation of D2R-Ca(v)1.3 caused depressed activity in the DMS during expression of habitual cocaine-seeking behavior. The imbalanced function between the DMS and DLS, which causes a shift from the DMS to the DLS, may mediate habitual behaviors. (C) 2017 Published by Elsevier Ltd on behalf of IBRO.