Involvement of the GABAB receptors in morphine antinociception in male and female mice: Pharmacological and genetic approaches

PEDRÓN VALERIA T.; VARANI ANDRÉS P.; BETTLER BERNHARD; BALERIO GRACIELA N.

Congreso; 10th FENS Forum of Neuroscience; 2016

Previous studies from our laboratory showed an interaction between the GABAergic and opioid systems involved in the analgesic effect of baclofen (BAC). Furthermore, it is known that sex differences exist with respect to various pharmacological responses of morphine (MOR) and they are related to an increased sensitivity to MOR effects in males. The aims of the present study were to evaluate sex differences and the possible involvement of the GABABreceptors in the antinociceptive responses induced by MOR (1, 3 and 9 mg/kg, sc) administration using both pharmacological (BAC 2 mg/kg, ip; and 2-OH-saclofen 0.3 mg/kg, intracisternamagna) and genetic approaches (GABAB1 knockout mice; KO). In addition, we explored the alterations in c-Fos expression of different brain areas involved in the antinociceptive effect of MOR using both approaches. The pharmacological approach showed a higher dose-dependent antinociceptive effect of MOR in male compared to female mice. BAC and SAC pretreatment potentiated and attenuated the antinociceptive effect of MOR, respectively, in both sexes. The genetic approach revealed a dose-dependent antinociceptive effect of MOR in the wild type mice, but not in the KO mice and no sex differences were observed. Additionally, BAC and SAC pretreatment and the lack of GABAB1 subunit of the GABABreceptor prevented the changes observed in c-Fos expression in the cingulate cortex and nucleus accumbens of male mice. Our results suggest that the GABAB receptors are involved in the MOR antinociceptive effect of both male and female mice.