Baclofen reestablishes the mu-opioid receptor levels modified by the morphine withdrawal syndrome in either sexes

Artículo

Resumen *

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 addition, we have demonstrated that BAC reestablishes the dopamine levels modified by MOR withdrawal syndrome in male mice. The aim of the present study was to evaluate the mu-opioid receptor binding parameters in striatum and frontal cortex of male and female mice during MOR withdrawal and its prevention with BAC. Prepubertal Swiss-Webster mice of either sex 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 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 the striatum and frontal cortex were dissected in order to perform binding studies with [3H][DAMGO]. The density of mu-opioid receptor increased significantly during MOR withdrawal in male and female striatum as well as in male cortex. In addition, in both brain areas the Bmax was higher in male than in female mice during MOR withdrawal. Finally, BAC pretreatment of MOR withdrawn mice reestablished the levels of mu-opioid receptor by significantly decreasing the Bmax in either sex. In conclusion, although there were sex differences in the mu-opioid receptor density during MOR withdrawal syndrome, BAC was able to reestablish the changes in binding parameters induced by the NALprecipitated withdrawal in female and male mice. Información suministrada por el agente en SIGEVA