The effects of systemic and intracerebral injections of D 1 and D 2 agonists on brain stimulation reward

Abstract

That dopamine (DA) plays a role in reward-related learning is well documented but the mechanisms through which it acts are not well understood. The present set of experiments investigated the role of DA receptor subtypes within DA-innervated forebrain regions in brain stimulation reward (BSR). Thirty-two rats were implanted with electrodes in the ventral tegmental area (VTA) and cannulae aimed at the caudal nucleus accumbens (NAcc), the caudate-putamen (CP) or cortex. Rate-frequency functions were determined by logarithmically decreasing the number of cathodal pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding (thresholds). After BSR thresholds stabilized rats received treatments with DA agonists and their effects on thresholds were analyzed. Systemic treatments consisted of injections of (+)-amphetamine (1.0 mg/kg, i.p., 10 min before testing), the D 2 agonist quinpirole (1.0 mg/kg, i.p., 10 min before testing), the novel D 1 agonist A-77636 (3.0 mg/kg, s.c., 90 min before testing) or their vehicle (distilled H 2O). Central treatments consisted of microinjections of quinpirole (0.3 – 10.0 μg/0.5 μl) directly into the caudal NAcc, CP or cortex or A-77636 (30 μg/0.5 μl) into 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. Central injections of quinpirole in the caudal NAcc, CP or cortex produced significant increases in BSR thresholds indicative of reduced rewarding efficacy of stimulation. Central injections of A-77636 into the caudal NAcc, but not the CP, were associated with a reduction in VTA BSR thresholds, suggesting an increase in reward. These results suggest that stimulation of D 1 or D 2 receptors enhances the rewarding effect of brain stimulation. In the case of the systemic quinpirole enhancement of reward, the present results suggest that this may not occur in the caudal NAcc, CP or cortex. Finally, the present results suggest that D 1 receptor stimulation in the caudal NAcc can facilitate reward-related learning.