A dopamine D-1 agonist elevates self-stimulation thresholds: Comparison toother dopamine-selective drugs

The effects of the high-efficacy D-1 receptor agonist SKF 81297 and the D-2 /3 receptor agonist 7-OH-DPAT on brain stimulation reward thresholds and on response latencies in responding for the stimulation, were compared to the effects of subtype-selective receptor antagonists and a dopamine uptake bl ocker. SKF 81297 produced dose-dependent elevations in reward thresholds bu t did not alter response latencies. In contrast, 7-OH-DPAT produced inconsi stent reward threshold elevations, yet dose dependently increased response latencies. Both the dopamine D1 receptor antagonist SCH 23390 and the D-2 a ntagonist raclopride elevated reward thresholds, but only raclopride signif icantly increased response latencies. The dopamine uptake inhibitor GBR 129 09 lowered reward thresholds and did not influence response latencies. The present results provide a clear demonstration that a selective, high-effica cy D-1 receptor agonist elevates brain stimulation reward thresholds withou t producing performance deficits. Furthermore, it was observed that the eff ects upon reward measures of D-1-selective compounds, but not D-2/D-3-selec tive compounds, are dissociable from their effects upon response latency in this task. These results are discussed with regard to a distinction betwee n the effects of indirect and direct dopamine agonists on reward thresholds , a distinction that does not depend upon the subtype-selectivity of the di rect agonists tested. (C) 1999 Elsevier Science Inc.