This study searched for sex-specific differences in the contribution of µ- , δ- and κ-opioid receptors in analgesic response evoked by stress. Opioid receptors are widely known to influence stress-induced analgesia. With the use of mouse lines selected for high and low swim stress-induced analgesia we show that males and females from both lines display similar analgesic responses. Antagonism of the 3-min swim-induced analgesia with prototypic opioid antagonist naloxone (10mg/kg i.p.) was less effective in females in these stress conditions. Further analysis using selective –mu (cyprodime), –delta (naltrindole) and –kappa (nor-binaltorphimine) opioid receptor antagonists (all 10mg/kg, i.p.) show that differences in the sensitivity to naloxone inhibition of SSIA may be caused by a higher involvement of the –delta opioid system and decreased functionality of –mu opioid analgesia. No sex differences in neurochemical mechanism of analgesia were also showed in the naloxone-resistant LA mice. We postulate that studies performed on mice with divergent opioid system activity are relevant in detection of tenuous sex differences in opioid analgesia.

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