• Jay C Elliott, Mitchell J Picker, Andrew J Sparrow, and Donald T Lysle.
• Department of Psychology, CB #3270, Davie Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA. elliojc@musc.edu
• Psychopharmacology (Berl.). 2006 Mar 1; 185 (1): 66-75.

RationaleThe sex of the individual can have a profound effect on sensitivity to the effects of opioids. Recently, our laboratory provided the first evidence that females may be more sensitive to the immune-altering effects of mu-opioids than males. However, it remains unknown whether kappa- and delta-opioids produce sexually dimorphic effects on immune responses.ObjectiveThe present study sought to determine whether kappa- and delta-opioids produce differential immunological effects in males and females using the memory-T-cell-dependent in vivo inflammatory response contact hypersensitivity (CHS). As sex differences in the magnitude of opioid effects can be outcome-specific, additional experiments were conducted to compare the immunological effects of kappa- and delta-opioids with other behavioral and physiological effects.Materials And MethodsContact hypersensitivity was induced in male and female Fischer rats. Prior to elicitation of CHS, animals were administered selected doses of the kappa-opioid spiradoline (0.2-20 mg/kg), delta-opioid SNC80 (1-10 mg/kg), or vehicle. The antinociceptive and diuretic effects of spiradoline were also assessed in males and females, as were the locomotor effects of SNC80.ResultsSpiradoline produced significantly greater enhancement of CHS in females than males, but produced comparable antinociceptive and diuretic effects in both sexes. By contrast, SNC80 did not significantly affect the course of CHS in either sex, but females were significantly more sensitive to its locomotor stimulatory effects.ConclusionsThese results demonstrate that females are more sensitive than males to the CHS-altering effects of spiradoline and that sex differences in the magnitude and direction of opioid-induced sex differences are outcome dependent.

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