Differential dose-dependent effects of central morphine treatment upon food intake in male and female rats receiving neonatal hormone manipulations.

Male rats display significantly greater analgesic responses following morphine than female rats, with neonatal gonadal manipulations reversing the sex-dependent pattern. The present study assessed whether dose-dependent (0.0005-5 microg, icv) effects of morphine-induced feeding were sensitive to sex-dependent and neonatal gonadectomy manipulations. Sex differences in morphine-induced feeding varied as a function of morphine dose with males showing greater increases at low (0.0005 microg) doses, and females showing greater increases at high (5 microg) doses. Neonatal castration, respectively, enhanced and reduced morphine-induced feeding at very low (0.0005 microg) and low (0.005 microg) doses. In contrast, neonatal testosterone administered to females enhanced morphine-induced feeding at higher (0.5-5 microg) doses. These data indicate that sex and neonatal gonadectomy differences in morphine-induced feeding are dependent upon the dose of morphine employed.

Reversal of sex differences in morphine analgesia elicited from the ventrolateral periaqueductal gray in rats by neonatal hormone manipulations.

Male rats display significantly greater analgesic responses than female rats following systemic, ventricular and intracerebral morphine administration into either the ventrolateral periaqueductal gray (vlPAG) or the rostral ventromedial medulla, and following beta-endorphin administration into the vlPAG. Although adult gonadectomy severely reduces nonopioid forms of swim stress-induced analgesia, the marked sex differences in morphine analgesia were minimally affected by either male or female adult gonadectomy. Since very little is known about neonatal effects of gonadal hormones upon sex differences in morphine analgesia elicited from the vlPAG, the present study evaluated the effects of neonatal (within 1 day of birth) castration in male rat pups relative to sham-operated controls, and systemic androgenization with testosterone propionate in female rat pups relative to vehicle-injected controls upon baseline nociceptive thresholds and morphine analgesia elicited from the vlPAG in rats tested as adults. Significant sex differences in morphine analgesia elicited from the vlPAG were observed with adult males receiving neonatal sham surgeries displaying significantly greater morphine analgesia on two nociceptive measures than adult females tested during the estrous phase and receiving neonatal vehicle injections. Neonatal gonadectomy essentially reversed the pattern of sex difference effects upon morphine analgesia elicited from the vlPAG. Neonatally-castrated male rats tested in adulthood displayed dramatic reductions in morphine analgesia elicited from the vlPAG on both the tail-flick (approximately 15-fold rightward shift) and jump (6-fold rightward shift) tests relative to sham-operated males, and essentially mirrored those of vehicle-treated females. Conversely, neonatally-androgenized female rats tested in adulthood displayed dramatic increases in morphine analgesia elicited from the vlPAG on the tail-flick (5-fold leftward shift) and jump (12-fold leftward shift) tests relative to vehicle-treated females, and approximated those observed in sham-operated males. The potent differences between neonatally-castrated and sham-operated male rats and between neonatally-androgenized and vehicle-treated female rats suggest a possible 'organizational' role of gonadal hormones in mediating sex differences in morphine analgesia elicited from the vlPAG.