EFFECTS OF THE DOPAMINE D-1 ANTAGONIST SCH-23390 MICROINJECTED INTO THE ACCUMBENS, AMYGDALA OR STRIATUM ON COCAINE SELF-ADMINISTRATION IN THE RAT

This study tested the hypothesis that blockade of D-1 dopamine recepto rs in the nucleus accumbens shell, central nucleus of the amygdala or dorsal striatum by intracerebral microinjection of the dopamine antago nist SCH 23390 produces an attenuation of the effects of self-administ ered cocaine. Microinjection of SCH 23390 (0-4.0 mu g total dose) into any of the three brain regions dose-dependently increased the rate of cocaine self-administration, consistent with a partial attenuation of the effects of cocaine under these conditions (0.25 mg cocaine i.v.; fixed-ratio 5 timeout 20 s). The regional rank order potency of SCH 23 390 was accumbens > amygdala > striatum, striatal injections being equ ipotent with subcutaneous administration. Moreover, SCH 23390 produced rapid effects on cocaine self-administration only when injected into the accumbens or amygdala. The time course of this regional selectivit y was consistent with the rate of diffusion of SCH 23390 from the site of injection as measured by quantitative autoradiography, demonstrati ng that the regional selectivity of intracerebral injections of SCH 23 390 is time-dependent. These results support a role for D-1 dopamine r eceptors in the nucleus accumbens and amygdala in the effects of self- administered cocaine, and suggest that D-1 receptors in certain portio ns of the 'extended amygdala' may be an important substrate for the re inforcing actions of cocaine.