Repeated 7-OH-DPAT treatments: behavioral sensitization,dopamine synthesis and subsequent sensitivity to apomorphine and cocaine |
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| Authors: | B. A. Mattingly S. E. Fields M. S. Langfels J. K. Rowlett P. M. Robinet M. T. Bardo |
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| Affiliation: | (1) Department of Psychology, Morehead State University, 40351-1689 Morehead, KY, USA;(2) Department of Psychiatry and Human Behavior, Arthur C. Guyton Laboratory Research Building, University of Mississippi Medical Center, 2500 North State Street, 39216-4505 Jackson, MS, USA;(3) Department of Psychology, University of Kentucky, 40506-0044 Lexington, KY, USA |
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| 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 due to the development of dopamine autoreceptor subsensitivity. |
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| Keywords: | Behavioral sensitization Cross-sensitization 7-OH-DPAT Cocaine Locomotor activity Dopamine D2-type receptors Dopamine D3 receptors |
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