Autoradiographic study of µ-opioid receptors in prepubertal mice of either sex during morphine withdrawal syndrome and its prevention with baclofen

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

Mar del Plata

Congreso; XXXVII Reunión Anual de Comunicaciones Científicas.; 2005

Sociedad Argentina de Farmacología Experimental

Autoradiographic study of µ-opioid receptors in prepubertal mice of either sex during morphine withdrawal syndrome and its prevention with baclofen. 1,2Diaz S, 3Barros V, 3Antonelli M, 1,2Rubio M, 1,2Balerio G. 1ININFA (CONICET), 2Cát. de Farmacología e 3IQUIFIB (FFyB, UBA) Junín 956, 1113, Bs. As., Argentina. sildiaz@ffyb.uba.ar We have previously shown that the GABAB agonist baclofen (BAC) attenuates the expression of naloxone (NAL)-precipitated morphine (MOR) withdrawal in male as well as female mice. In order to extend these observations, our aim was to analyze μ-opioid binding sites in various brain areas in mice of either sex during MOR withdrawal and its prevention with BAC. Prepubertal Swiss mice were rendered dependent by i.p. injection of MOR (2 mg/kg) twice daily for 9 days. On the 10th day, dependent mice 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. Mice were sacrificed, brains were collected and different areas were dissected to perform autoradiographic studies with [3H]-DAMGO. The µ-opioid labeling significantly increased in caudate putamen (CPu), nucleus accumbens core (NAcC), mediodorsal thalamic nucleus (MDTh), basal amygdala and ventral tegmental area of MOR withdrawn males vs control groups. Conversely, opiate receptor labeling was not modified in any of the areas studied of females. BAC reestablished µ-opioid receptor levels modified by MOR withdrawal only in CPu, NAcC and MDTh of males. The sexual dimorphism observed herein confirms the greater sensitivity of males in response to MOR. Our results also suggest that the effect of BAC in preventing the expression of MOR withdrawal signs could be related with its ability to reestablish the µ-opioid receptor labeling in certain brain areas.