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Abstract
In cultured rat striatal neurons exposed to 10 μM morphine or oxotremorine for 24 hours, we observed an increased (about 30 %) dopamine D 1 receptor-stimulated cyclic AMP production, whereas no desensitization of μ-opioid receptor or muscarinic cholinergic receptor was found. However, whereas upregulation of dopamine D 1 receptor-stimulated adenylate cyclase activity upon 7 days morphine exposure was at least as pronounced as observed after 24 hours of exposure to the opioid, this adaptive phenomenon was virtually absent following one week of oxotremorine treatment. This reduced adenylate cyclase sensitization upon 7 days oxotremorine exposure appeared to coincide with desensitization of muscarinic cholinergic receptors. A possible role of the resistance of μ receptors to desensitization and the (resulting) upregulation of the neuronal adenylate cyclase system upon chronic receptor activation in the development of opiate tolerance and dependence is suggested.
Published Version
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