Effects of pharmacological blockade of MC1Rs by the peptide antagonist, Ac-Nle-Asp-Trp-DPhe-Nle-Trp-Lys-NH2 (ANT; 20 μg per mouse, i.c.v.), on the magnitude and MK-801 sensitivity of U50,488 analgesia in mice of both sexes. Bars represent mean ± SEM percent total analgesia (% analgesia) over the 60-min testing period. The outbred Crl:CD-1 mice used in this experiment were even less sensitive to U50,488 than C57BL/6 mice (see Fig. 2), but also displayed a quantitative sex difference in analgesic magnitude (P < 0.001). There was no evidence of analgesia from the ANT alone in either sex (data not shown). n = 4–6 mice per condition. These data have been replicated in a separate laboratory (not shown). *, Significantly lower than corresponding saline group, P < 0.001. †, Significantly higher than corresponding vehicle group, P < 0.001.