Sex and genotype specificity of U50,488 analgesia dose–response relationships (10–70 mg/kg, i.p.), and the antagonistic effect of the NMDA antagonist, MK-801 (0.075 mg/kg, s.c.), in male and female mice with functional (B6, a and b) or nonfunctional (e/e, c and d) MC1Rs. Symbols (●, saline-treated; ○, MK-801-treated) represent mean ± SEM percent total analgesia (% analgesia) over the 60-min testing period. No differences were observed in baseline nociceptive sensitivity among genotypes (P = 0.12); males of both genotypes had modestly but significantly increased latencies relative to females (P < 0.005). n = 4–11 mice per genotype per sex per dose; these data have been replicated with equivalent sample sizes (not shown). See Table 1 for AD50 estimates calculated from these data.