Morphine withdrawal syndrome and its prevention with baclofen: autoradiographic study of µ-opioid receptors in prepubertal mice of either sex

DIAZ S, BARROS V, ANTONELLI M, RUBIO M, BALERIO G

Washington, DC, USA

Congreso; 35th Annual Meeting Society for Neuroscience; 2005

Morphine withdrawal syndrome and its prevention with baclofen: autoradiographic study of µ-opioid receptors in prepubertal mice of either sex. 1,2Diaz S, 3Barros V, 3Antonelli M, 1,2Rubio M, *1,2Balerio G 1Cátedra de Farmacología, FFyB (UBA), buenos aires, Argentina 2ININFA (CONICET), Buenos Aires, Argentina 3IQUIFIB, FFyB, (UBA), Buenos Aires, Argentina *e-mail: gbalerio@ffyb.uba.ar   We have previously shown that the GABAB agonist baclofen (BAC) prevents the expression of morphine (MOR) withdrawal syndrome in male as well as female mice. In order to extend these previous observations, the aim of the present study was to evaluate the density of µ-opioid receptors in various brain areas in mice of either sex during MOR withdrawal and its prevention with BAC. Prepubertal Swiss-Webster mice were rendered dependent by intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 days. On the tenth day, dependent animals received 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 different brain areas were dissected in order to perform autoradiographic studies with [3H]-[DAMGO]. Autoradiographic mapping showed a significant increase of µ-opioid receptor density during MOR withdrawal in nucleus accumbens core (NAcC), caudate putamen (CPu), mediodorsal thalamic nucleus (ThNu), basolateral amygdala (BLA), basomedial amygdala (BMA) and ventral tegmental (VTA) area vs respective saline control groups, in male mice. In contrast, opiate receptor labeling was not modified in any of the brain areas studied in female mice. BAC was able to reestablish µ-opioid receptor density during MOR withdrawal only in NAcC, CPu and ThNu of males. The structural sexual dimorphism observed in the present study confirms previous reports indicating a greater sensitivity of males in response to MOR pharmacological properties. The present results suggest that the effect of BAC in preventing the expression of MOR withdrawal signs, could be related with the ability of BAC to reestablish the µ-opioid receptor density in certain brain areas.