Inhibition by MK-801 of cocaine-induced sensitization, conditioned place preference, and dopamine-receptor supersensitivity in mice |
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Authors: | Hack-Seang Kim Woo-Kyu Park Choon-Gon Jang Seikwan Oh |
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Institution: | aDepartment of Pharmacology, College of Pharmacy, Chungbuk National University, Cheongju 360-763, Korea;bKorea Research Institute of Chemical Technology, Taejon 305-606, Korea;cDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216-4045, USA |
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Abstract: | Repeated administration of cocaine led to increases in ambulation-accelerating activity (sensitization) and conditioned place preference (CPP). Dopamine (DA)-receptor supersensitivity was also developed in cocaine-induced sensitized and CPP mice. An N-methyl-d-aspartate (NMDA)-receptor antagonist, MK-801, blocked simultaneously developments of cocaine-induced behavioral sensitization, CPP, and DA-receptor supersensitivity. Furthermore, MK-801 inhibited a apomorphine-induced striatal dopaminergic action: climbing behavior. These results suggest that the cocaine-induced dopaminergic behaviors such as sensitization to ambulatory activity and CPP may be produced via activation of the NMDA receptor. The development of postsynaptic DA-receptor supersensitivity may be an underlying common mechanism that mediates cocaine-induced behavioral sensitization and CPP. |
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Keywords: | Behavioral sensitization Place conditioning Dopamine-receptor supersensitivity Cocaine MK-801 |
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