Baclofen re-establishes mu-opioid receptor levels modified by

S. DIAZ, A. KEMMLING, C. BONAVITA, M. RUBIO AND G. BALERIO

New York, USA

Congreso; 35th Annual Meeting, American Society of Neurochemistry; 2004

Baclofen reestablishes m-opioid receptor levels modified by morphine withdrawal syndrome in either sexes S.L. Diaz, A.K. Kemmling, C.D. Bonavita, M.C. Rubio and G.N. Balerio. Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires; Instituto de Investigaciones Farmacológicas, CONICET, Junín 956, 5º floor, (1113AAD), Buenos Aires, Argentina. Phone: 54 11 4961 5949. FAX: 54 11 4963 8593. sildiaz@ffyb.uba.ar We have previously shown that the GABAB agonist baclofen (BAC) prevents the expression of the morphine (MOR) withdrawal syndrome in mice of either sexes. We have also demonstrated that BAC reestablishes the dopamine levels modified by the MOR withdrawal syndrome in male mice. The aim of this study was to evaluate μ-opioid receptor binding parameters in striatum and frontal cortex of male and female mice during MOR withdrawal and its prevention with BAC. Prepuberal Swiss-Webster mice of either sexes were rendered dependent by intraperitoneal (i.p.) injection of MOR (2 mg/kg) twice daily for 9 days. On the 10th day, dependent animals received naloxone (NAL) (6 mg/kg, i.p.) 60 min after the last dose of MOR and another pool of dependent mice received BAC (2 mg/kg, i.p.) previous to NAL injection. Thirty min after NAL or saline injection mice were sacrificed, brains were collected and striatum and frontal cortex were dissected in order to perform binding studies with [3H][DAMGO]. The density of μ-opioid receptor increased significantly during MOR withdrawal in male and female striatum and in male cortex. In both brain areas, Bmax was higher in males than in females. Finally, BAC pretreatment reestablished the levels of μ-opioid receptor by significantly decreasing the Bmax in either sexes. In conclusion, although there were sex differences in the μ-opioid receptor density during the MOR withdrawal syndrome, BAC was able to reestablish the changes in binding parameters induced by the NAL-precipitated withdrawal in either sexes.