Abstract

The available evidence suggests that daily injections of selective dopamine (DA) D2 receptor agonists to DA depleted rats typically leads to behavioral sensitization, but the effects of repeated treatment with selective DA D1 receptor agonists are more equivocal. In this study we examined the effects of acute and repeated treatment with DA receptor agonists with various D1/D2 receptor selectivities on rotation and striatal c-fos activation in rats with unilateral DA depletions. Lesioned rats were treated daily for 10 d with either the novel, selective DA D1 receptor agonist, A-85653, the DA D2 receptor agonist, quinpirole, a combination of these compounds, or the indirect D1/D2 receptor agonist levodopa (L-DOPA). Over days, rats given A-85653 alone showed behavioral tolerance, whereas those given either quinpirole or L-DOPA demonstrated behavioral sensitization. Repeated A-85653 + quinpirole treatment s lead to an increase in response magnitude early in the testing sessions and this was accompanied by a reduction in response duration over days. Quantitative analysis of striatal c-fos activation was also conducted in lesioned rats treated acutely or repeatedly with A-85653, A-85653 + quinpirole or L-DOPA. Numbers of Fos-immunoreactive nuclei were sharply reduced after the agonist challenge in all animals given repeated, compared to acute, drug treatment, despite enhanced levels of rotation by rats given quinpirole + A-85653 or L-DOPA repeatedly. These results suggest that desensitization may develop at the DA D1 receptor as a consequence of repeated stimulation, and that the behavioral sensitization seen after repeated L-DOPA treatment may primarily involve the DA D2 receptor.