Drug seeking under the control of drug-associated stimuli and its reinstatement after extinction can be decreased by systemic administration of dopamine D3 receptor antagonists. It is demonstrated that responding by rats on the active lever for cocaine under a 2nd-order schedule of reinforcement, under which responding is maintained by response-contingent cocaine-paired conditioned reinforcers, is markedly attenuated by infusion of the dopamine D3 receptor antagonist SB-277011-A into the amygdala (2 and 4 microg/0.3 microl). By contrast, infusions of SB-277011-A into the shell subregion of the nucleus accumbens and also into the dorsal striatum were without effect. These results show that the control over drug seeking by conditioned reinforcers depends on D3 receptor-dependent dopamine transmission in the amygdala.
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