ROTATION AND STRIATAL C-FOS EXPRESSION AFTER REPEATED, DAILY TREATMENT WITH SELECTIVE DOPAMINE-RECEPTOR AGONISTS AND LEVODOPA

The available evidence suggests that daily injections of selective dop amine (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 st riatal c-fos activation in rats with unilateral DA depletions. Lesione d 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 agon ist levodopa (L-DOPA). Over days, rats given A-85653 alone showed beha vioral tolerance, whereas those given either quinpirole or L-DOPA demo nstrated behavioral sensitization. Repeated A-85653 + quinpirole treat ment lead to an increase in response magnitude early in the testing se ssions and this was accompanied by a reduction in response duration ov er days. Quantitative analysis of striatal c-fos activation was also c onducted in lesioned rats treated acutely or repeatedly with A-85653, A-85653 + quinpirole or L-DOPA. Numbers of Fos-immunoreactive nuclei w ere sharply reduced after the agonist challenge in all animals given r epeated, compared to acute, drug treatment, despite enhanced levels of rotation by rats given quinpirole + A-85653 or L-DOPA repeatedly. The se results suggest that desensitization may develop at the DA D1 recep tor as a consequence of repeated stimulation, and that the behavioral sensitization seen after repeated L-DOPA treatment may primarily invol ve the DA D2 receptor.-