Repeated 7-OH-DPAT reatments: behavioral sensitizationdopamine synthesis and subsequent sensitivity to apomorphine and cocaine

Document Type

Article

Publication Date

1996

Abstract

Male Wistar rats (250 350 g) were injected(SC) daily with the putative selective dopamine D3 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 20 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 mesolimbic (nucleus accumbens-olfactory turbercle) tissue was assessed following acute or chronic 7-OH-DPAT treatments by measuring the accumulation of dihydroxyphenylalanine(DOPA) after treatment with a DOPA decarboxylase inhibitor. Major findings were as follows: a) acute 7-OH-DPAT 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 progressively greater increase in activity across the 10 test days (i.e., behavioral sensitization); c) subchronic treatment with 7-OH-DPAT did 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 synthesis in either brain region. Although the behavioral effects of 7-OH-DPAT were similar to the reported effects of the D2/D3 dopamine agonist quinpirole, the effects of repeated 7-OH-DPAT treatments differed from those of quinpirole in terms of cross-sensitization and basal dopamine synthesis. These results suggest that locomotor inhibition produced 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 dueto the development of dopamine autoreceptor sub-sensitivity.

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