6-HYDROXYDOPAMINE LESION OF VENTRAL PALLIDUM BLOCKS ACQUISITION OF PLACE PREFERENCE CONDITIONING TO COCAINE

In parallel with nucleus accumbens (NAS), ventral pallidum (VP) also r eceives a dopaminergic projection from the ventral tegmental area (VTA ). The present study examined the involvement of this mesopallidal dop aminergic system in the action of cocaine. In the first experiment, th e effect of cocaine injections on VP dopamine was examined by microdia lysis. Intraperitoneal (i.p.) injections of cocaine 5-20 mg/kg dose-de pendently increased the extracellular dopamine level in VP 2.5-4.5-fol d. In addition, intra-VP perfusion of 20 mu M cocaine induced a 12-fol d increase of dopamine locally. The second experiment examined the rol e of VP dopamine in cocaine-induced conditioned place preference (CPP) and locomotor activation. Rats received bilateral intra-VP injections of 3-4 mu g 6-OHDA or ascorbic acid vehicle in 0.5 mu l volume. Tissu e assays indicated that the 6-OHDA-lesioned rats had significantly low ered dopamine concentration in VP, but not in NAS or striatum. As a gr oup, 6-OHDA lesions blocked the development of CPP to 5 mg/kg cocaine but not to 10 mg/kg cocaine. However, rats with more than 60% depletio n in VP dopamine did not develop CPP to cocaine at either dose. Prefer ence for the cocaine-paired side correlated significantly with dopamin e concentration in VP, but not in NAS or striatum, It was concluded th at VP dopamine may play a critical role in the initial rewarding effec t of cocaine. 6-OHDA lesions also blocked locomotor activation induced by 5 mg/kg cocaine but had no effect on 10 mg/kg cocaine-induced loco motion. Dopamine concentration in VP did not correlate with the locomo tor activation response to cocaine at either dose. These findings furt her establish the involvement of the mesopallidal dopaminergic system in the action of cocaine.