Morphine withdrawal syndrome ans its prevention with baclofen: autoradiographic study of mu- opioids receptor in prepubertal male and female mice

DIAZ S., BARROS V.,ANTONELLI MC.,RUBIO MC., BALERIO GN.

SYNAPSE

Año: 2006 vol. 60 p. 132 - 140

0887-4476

    ABSTRACT Although the expression of the morphine (MOR) withdrawal syn­drome is more marked in male mice than in females, we have demonstrated that the GABAB agonist baclofen (BAG) is able to attenuate MOR withdrawal signs in either sex. In order to extend these previous observations, the aim of the present study was to evaluate the u-opioid receptor labeling in various brain areas in mice of either sex, during MOR withdrawal and its prevention with BAG. Prepubertal Swiss-Webster mice were rendered dependent by intraperitonial (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 MOR, and another pool of dependent mice received BAG (2 mg/kg, i.p.) previous to NAL. Thirty minutes after NAL, mice were sacrificed and autoradiography with [3HJ-[D-Ala2, A^Me-Phe4, -glycol5] enkephalin (DAMGO) was carried out on mice brains at five different anatomical levels. Autoradiographic map­ping showed a significant increase of u-opioid receptor labeling during MOR with­drawal in nucleus accumbens core (NAcC), caudate putamen (CPu), mediodorsal tha-lamic nucleus (MDTh), basolateral and basomedial amygdala, and ventral tegmental area vs. respective control groups in male mice. In contrast, opiate receptor labeling was not significantly modified in any of the brain areas studied in withdrawn females. BAG reestablished u-opioid receptor binding sites during MOR withdrawal only in NAcC of males, and a similar tendency was observed in CPu and MDTh, even when it was not statistically significant. The 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 BAG in pre­venting the expression of MOR withdrawal signs could be related with the ability of BAG to reestablish the u-opioid receptor labeling in certain brain areas. Synapse 60:132-140, 2006. 02006 Wiiey-Liss, inc.