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

Sex differences have been observed in antinociception after morphine admini stered into either the lateral ventricles, rostral ventromedial medulla, or ventrolateral periaqueductal gray such that male rats exhibit significantl y greater antinociception than female rats. Adult gonadectomy produced smal l, but significant changes in morphine antinociception relative to same-sex sham-operated controls. The present study examined whether sex and adult g onadectomy differences were observed in antinociceptive responses after D-P ro(2)-Endomorphin-2 (1-50 mu g) elicited from the ventrolateral periaqueduc tal gray (vIPAG) on the tail-flick and jump tests in rats, and compared the se effects with morphine antinociception. D-Pro(2)-Endomorphin-2 antinocice ption in the vIPAG was significantly greater in estrous-phase, sham-operate d and ovariectomized female rats relative to sham-operated and castrated ma le rats on the tail-flick, but not jump test that differed markedly from th e greater magnitude of morphine antinociception noted for male rats on both tests. In testing whether D-Pro(2)-Endomorphin-2's antinociceptive sex dif ferences were secondary to alterations in activity, similar decreases in th e pattern of total activity were observed after D-Pro(2)-Endomorphin-2 in t he vIPAG in male and female rats. In evaluating whether male and female rat s differed in their behavioral activation responses after D-Pro(2)-Endomorp hin-2 in the vIPAG, significantly more excessive grooming, seizures, barrel rolls and explosive running behaviors were observed after D-Pro(2)-Endomor phin-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 vIPAG appear to be attributable to sex-dependent alter ations in behavioral activation rather than nociceptive processing per se. (C) 2000 Elsevier Science Inc. All rights reserved.