Sex Difference in  -Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5'-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig (original) (raw)

2011, Journal of Pharmacology and Experimental Therapeutics

We examined if sex differences in KOPR pharmacology exists in guinea pigs, which are more similar to humans in the expression level and distribution of KOPR in the brain than rats and mice. The KOPR agonist U50,488H produced a dose-dependent increase in abnormal postures and immobility with greater effects in males than females. Males also showed greater U50,488H-induced antinociception in the paw pressure test than females. Pretreatment with KOPR antagonist norBNI blocked U50,488H-induced abnormal body postures and antinociception. In contrast, inhibition of cocaine-induced hyperactivity by U50,488H was more effective in females than males. Thus, sex differences in the effects of U50,488H are endpoint-dependent. We then examined if sex differences in KOPR level and KOPR-mediated G protein activation in brain regions may contribute to the observed differences using quantitative in vitro autoradiography of [ 3 H]U69,593 binding to the KOPR and U50,488H-stimulated [ 35 S]GTPS binding. Compared to females, males exhibited greater [ 3 H]U69,593 binding in the deep layers of somatosensory and insular cortices, claustrum, endopiriform nucleus, periaqueductal gray, and substantial nigra. Concomitantly, U50,488H-stimulated [ 35 S]GTPS binding was greater in males than females in the superficial and deep layers of somatosensory and insular cortices, caudate putamen, claustrum, medial geniculate nucleus and cerebellum. In contrast, compared to males, females showed greater U50,488Hstimulated [ 35 S]GTPS binding in the dentate gyrus, and a trend of higher [ 35 S]GTPS binding in the hypothalamus. These data demonstrate that males and females differ in KOPR expression and KOPR-mediated G-protein activation in distinct brain regions, which may contribute to the observed sex differences in KOPR-mediated pharmacology.