Antinociceptive and behavioral activation responses elicited by d-Pro(2)-endomorphin-2 in the ventrolateral periaqueductal gray are sensitive to sex and gonadectomy differences in rats.

摘要

Sex differences have been observed in antinociception after morphine administered into either the lateral ventricles, rostral ventromedial medulla, or ventrolateral periaqueductal gray such that male rats exhibit significantly greater antinociception than female rats. Adult gonadectomy produced small, but significant changes in morphine antinociception relative to same-sex sham-operated controls. The present study examined whether sex and adult gonadectomy differences were observed in antinociceptive responses after D-Pro(2)-Endomorphin-2 (1-50 microg) elicited from the ventrolateral periaqueductal gray (vlPAG) on the tail-flick and jump tests in rats, and compared these effects with morphine antinociception. D-Pro(2)-Endomorphin-2 antinociception in the vlPAG was significantly greater in estrous-phase, sham-operated and ovariectomized female rats relative to sham-operated and castrated male rats on the tail-flick, but not jump test that differed markedly from the greater magnitude of morphine antinociception noted for male rats on both tests. In testing whether D-Pro(2)-Endomorphin-2's antinociceptive sex differences were secondary to alterations in activity, similar decreases in the pattern of total activity were observed after D-Pro(2)-Endomorphin-2 in the vlPAG in male and female rats. In evaluating whether male and female rats differed in their behavioral activation responses after D-Pro(2)-Endomorphin-2 in the vlPAG, significantly more excessive grooming, seizures, barrel rolls and explosive running behaviors were observed after D-Pro(2)-Endomorphin-2 in male, but not female rats during the precise periods of time when they were failing to display robust antinociceptive responses on the tail-flick test. Thus, the different patterns of sex differences after D-Pro(2)-Endomorphin-2 in the vlPAG appear to be attributable to sex-dependent alterations in behavioral activation rather than nociceptive processing per se.