Qualitative sex differences in kappa-opioid analgesia in mice are dependent on age

Neurosci Lett. 2004 Jun 10;363(2):178-81. doi: 10.1016/j.neulet.2004.04.004.


The effects of aging on sex differences in analgesia from the kappa-opioid agonist, U50,488H (U50), were examined in C57BL/6J mice. U50 analgesia can be blocked by the N-methyl-d-aspartate receptor antagonist, MK-801 (MK), in male rodents and gonadectomized females, but not hormonally intact or estrogen-replaced females, suggesting the existence of alternate neurochemical mediation in females. We now report that MK antagonism of U50 analgesia is age-dependent in females. That is, reproductively senescent females display MK-sensitive U50 analgesia qualitatively similar to that displayed by males or hormonally deprived young females. Age-related reductions in U50 analgesic magnitude were also observed in females. Thus, age and gender are likely to alter the clinical efficacy of analgesic drugs active at kappa-opioid receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / antagonists & inhibitors
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Aging / metabolism*
  • Analgesics, Non-Narcotic / pharmacology
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Resistance / physiology
  • Estrous Cycle / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Gonadal Steroid Hormones / metabolism
  • Menopause / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pain / drug therapy
  • Pain / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Opioid, kappa / drug effects*
  • Receptors, Opioid, kappa / metabolism
  • Sex Characteristics*


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Excitatory Amino Acid Antagonists
  • Gonadal Steroid Hormones
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid, kappa
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer