2 DISCRETE NUCLEUS-ACCUMBENS PROJECTION AREAS DIFFERENTIALLY MEDIATE COCAINE SELF-ADMINISTRATION IN THE RAT

The region of the nucleus accumbens and its connections have been impl icated in the reinforcing actions of cocaine as measured by intra-veno us self-administration. Our previous work has demonstrated that iboten ic acid lesions of one of the output regions of the nucleus accumbens, the sublenticular region of the extended amygdala (SEA), resulted in significant decreases in the highest ratio obtained in rats self-admin istering cocaine. In the present study, the importance of another nucl eus accumbens output, the subcommissural ventral pallidum (SVP), in me diating the self-administration of cocaine in the rat was explored. An imals were trained to self administer cocaine (0.75 mg/kg/inj) via an intravenous catheter on a FR5 schedule of reinforcement. Subsequently, subjects were either given bilateral intracerebral injections (0.5 mu l per side) of ibotenic acid (10 mug/mul lesion group) or vehicle (sha m group) into the SVP or into the SEA. Four days postlesion, cocaine s elf-administration on a FR5 schedule was resumed for 3 days. Next, a d ose effect function was determined in one 3-h session. Finally, a prog ressive ratio probe in which the ratio requirement was increased after each reinforcement was tested. Lesions of both the SVP and the SEA pr oduced significant changes in responding for intravenous cocaine on a FR5 schedule of reinforcement as compared to sham lesioned controls, a lthough the effect was found to be greater for the rats bearing lesion s of the SEA. While the lesions produced decreases in responding for c ocaine at all doses tested in the dose-effect function, the rate of re sponding was still inversely proportional to the dose in both groups. Compared to sham-lesioned animals in the progressive ratio task, SVP-l esioned rats did not differ from controls in the highest ratio complet ed for cocaine. On the other hand, lesions of the SEA, produced signif icant decreases in the breaking point as compared to sham-lesioned con trols. These results suggest that the sublenticular extended amygdala, which receives projections from the shell of the nucleus accumbens ma y be important in processing the reinforcing actions of cocaine.