THE EFFECTS OF SYSTEMIC AND INTRACEREBRAL INJECTIONS OF D-1 AND D-2 AGONISTS ON BRAIN-STIMULATION REWARD

That dopamine (DA) plays a role in reward-related learning is well doc umented but the mechanisms through which it acts are not well understo od. The present set of experiments investigated the role of DA recepto r subtypes within DA-innervated forebrain regions in brain stimulation reward (BSR). Thirty-two rats were implanted with electrodes in the v entral tegmental area (VTA) and cannulae aimed at the caudal nucleus a ccumbens (NAcc), the caudate-putamen (CP) or cortex. Rate-frequency fu nctions were determined by logarithmically decreasing the number of ca thodal pulses in a stimulation train from a value that sustained maxim al responding to one that did not sustain responding (thresholds). Aft er BSR thresholds stabilized rats received treatments with DA agonists and their effects on thresholds were analyzed. Systemic treatments co nsisted of injections of (+)-amphetamine (1.0 mg/kg, i.p., 10 min befo re testing), the D-2 agonist quinpirole (1.0 mg/kg, i.p., 10 min befor e testing), the novel D-1 agonist A-77636 (3.0 mg/kg, s.c., 90 min bef ore testing) or their vehicle (distilled H2O). Central treatments cons isted of microinjections of quinpirole (0.3-10.0 mu g/0.5 mu l) direct ly into the caudal NAcc, CP or cortex or A-77636 (30 mu g/0.5 mu l) in to the caudal NAcc or CP. Results showed that all three agonists, when injected systemically, significantly reduced the threshold frequency required for VTA BSR, indicating a potentiative effect on reward. Cent ral injections of quinpirole in the caudal NAcc, CP or cortex produced significant increases in BSR thresholds indicative of reduced rewardi ng efficacy of stimulation. Central injections of A-77636 into the cau dal NAcc, but not the CP, were associated with a reduction in VTA BSR thresholds, suggesting an increase in reward. These results suggest th at stimulation of D-1 or D-2 receptors enhances the rewarding effect o f brain stimulation. In the case of the systemic quinpirole enhancemen t of reward, the present results suggest that this may not occur in th e caudal NAcc, CP or cortex. Finally, the present results suggest that D-1 receptor stimulation in the caudal NAcc can facilitate reward-rel ated learning.