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Sex differences have been observed in antinociception following central administration of morphine into either the lateral ventricles or rostral ventromedial medulla (RVM) such that male rats exhibit significantly greater antinociception than female rats. The present study examined whether sex and adult gonadectomy differences were observed in morphine-induced (1–10 μg) antinociception elicited from the ventrolateral periaqueductal gray (vlPAG) on two nociceptive measures. Both sham-operated (ED₅₀=1.20–1.60 μg) and castrated (ED₅₀=1.08–1.09 μg) male rats displayed significantly greater magnitudes and potencies of morphine-induced antinociception on both tests than female rats. Sham-operated female rats tested during the estrous phase (ED₅₀=>50 μg) were significantly less sensitive to morphine than ovariectomized female rats (ED₅₀=1.98–2.51 μg). Thus, the vlPAG, a site sensitive to interactions …