EFFECTS OF LESIONS OF THE NUCLEUS BASALIS MAGNOCELLULARIS ON THE ACQUISITION OF COCAINE SELF-ADMINISTRATION IN RATS

The nucleus basalis magnocellularis (NBM) is one element in the limbic cortical-ventral striatal circuitry that has been implicated in reinf orcement processes. The present study examined the involvement of the cholinergic neurons of the NBM in mediating aspects of cocaine reinfor cement. Lesions of the NBM were made by injecting 0.01 M AMPA into the subpallidal basal forebrain. Following 4 days' recovery, rats were im planted chronically with catheters in the jugular vein. In three separ ate experiments, rats were trained to acquire cocaine self-administrat ion under a FR1 schedule of reinforcement at doses of 0.25, 0.083 and 0.028 mg/injection. A dose-effect function was also determined at the end of the acquisition experiments using five different doses of cocai ne (0.009, 0.028, 0.083, 0.25, 0.50 mg/injection) and saline which wer e presented once daily in a Latin square design. There were no signifi cant differences between groups in the acquisition of cocaine self-adm inistration at any of the three doses studied (0.028, 0.083 and 0.25 m g/injection), although at the lowest dose, lesioned animals responded at greater levels on both active and inactive levers. However, a shift to the left in the cocaine dose-response function was observed reveal ing that the lesioned group self-administered significantly higher amo unts of low doses of cocaine than control rats. These data suggest tha t the integrity of the NBM is not a critical determinant of the reinfo rcing effects of cocaine during the acquisition of self-administration of the drug, but that NBM-dependent cholinergic mechanisms may nevert heless interact with the neural substrates mediating the reinforcing p roperties of cocaine. The data are relevant to recent hypotheses of fu nctional interactions between the dopaminergic system and the choliner gic NBM.