EFFECTS OF DOPAMINERGIC AND GLUTAMATERGIC RECEPTOR ANTAGONISTS ON THEESTABLISHMENT AND EXPRESSION OF CONDITIONED LOCOMOTION TO COCAINE IN RATS

A series of experiments were conducted to investigate the role of dopa minergic D-1 and D-2 and glutamatergic NMDA and AMPA/kainate receptors on the establishment and expression of cocaine-induced conditioned lo comotion in rats. In the first experiment conditioned locomotion was d emonstrated by testing the animals in an environment previously associ ated with 15 mg/kg i.p. cocaine. The D-2-receptor antagonist (-)-sulpi ride (50 and 100 mg/kg i.p.) administered before cocaine during the co nditioning phase did not modify the establishment of conditioned locom otion whereas when administered before testing only at the higher dose it partially reduced rats' locomotion in the absence of cocaine (expr ession). At the higher dose (0.1 mg/kg i.p.) the D-1-receptor antagoni st SCH 23390 attenuated the expression of cocaine-induced conditioned locomotion whereas the lower dose (0.03 mg/kg i.p.) had no effect. Bot h doses of the NMDA receptor antagonist MK-801 (0.125 and 0.25 mg/kg i .p.) blocked the development of cocaine-induced conditioned locomotion but neither dose, when administered before testing, modified locomoti on in the absence of cocaine. Both doses of the AMPA/kainate receptor antagonist DNQX administered intracerebroventricularly (1 and 3 mu g/r at) blocked cocaine-induced conditioned locomotion when given before c ocaine during conditioning but when given before testing only the high er dose attenuated the conditioned activity. The results confirm the i mportance of the interaction between glutamatergic and dopaminergic sy stems for the conditional factors maintaining drug seeking behaviour. The findings may have implications for the treatment of cocaine cravin g and relapse.