REPEATED 7-OH-DPAT TREATMENTS - BEHAVIORAL SENSITIZATION, DOPAMINE SYNTHESIS AND SUBSEQUENT SENSITIVITY TO APOMORPHINE AND COCAINE

Male Wistar rats (250-350 g) were injected (SC) daily with the putativ e selective dopamine D-3 receptor agonist, 7-OH-DPAT (0.01, 0.10, or 1 .0 g/kg) or vehicle for 10 days, Fifteen minutes after each injection, the rats were tested for locomotor activity in photocell arenas for 2 0 min or 2 h. In two experiments, following this subchronic treatment, all rats received a challenge injection of apomorphine (1.0 mg/kg, SC ), or cocaine (10 mg/kg, IP) on day 11, and were tested for locomotor activity. In a third experiment, dopamine synthesis in striatal and me solimbic (nucleus accumbens-olfactory turbercle) tissue was assessed f ollowing acute or chronic 7-OH-DPAT treatments by measuring the accumu lation of dihydroxyphenylalanine (DOPA) after treatment with a DOPA de carboxylase inhibitor. Major findings were as follows: a) acute 7-OH-D PAT treatment produced a dose-dependent decrease in locomotor activity ; b) when tested for 2 h, the 1.0 mg/kg dose of 7-OH-DPAT produced a p rogressively greater increase in activity across the 10 test days (i.e ., behavioral sensitization); c) subchronic treatment with 7-OH-DPAT d id not result in cross-sensitization to either apomorphine or cocaine; d) acute treatment with the 1.0 mg/kg dose of 7-OH-DPAT significantly decreased dopamine synthesis in both striatal and mesolimbic regions; and e) chronic 7-OH-DPAT treatments did not affect basal dopamine syn thesis in either brain region. Although the behavioral effects of 7-OH -DPAT were similar to the reported effects of the D-2/D-3 dopamine ago nist quinpirole, the effects of repeated 7-OH-DPAT treatments differed from those of quinpirole in terms of cross-sensitization and basal do pamine synthesis. These results suggest that locomotor inhibition prod uced by low doses of 7-OH-DPAT is not related to dopamine autoreceptor stimulation, and the development of behavioral sensitization to high doses of 7-OH-DPAT is not due to the development of dopamine autorecep tor subsensitivity.