Basal Signaling Activity of   Opioid Receptor in Mouse Brain: Role in Narcotic Dependence (original) (raw)

2003, Journal of Pharmacology and Experimental Therapeutics

Narcotic analgesics cause addiction by poorly understood mechanisms, involving opioid receptor (MOR). Previous cell culture studies have demonstrated significant basal, spontaneous MOR signaling activity, but its relevance to narcotic addiction remained unclear. In this study, we tested basal MORsignaling activity in brain tissue from untreated and morphinepretreated mice, in comparison to antagonist-induced withdrawal in morphine-dependent mice. Using guanosine 5Ј-O-(3-[ 35 S]thio)triphosphate ([ 35 S]GTP␥S) binding and adenylyl cyclase activity assay in brain homogenates, we demonstrated that morphine pretreatment of mice enhanced basal MOR signaling in mouse brain homogenates and, moreover, caused persistent changes in the effects of naloxone and naltrexone, antagonists that elicit severe withdrawal in dependent subjects.

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