Qualitative sex differences in kappa-opioid analgesia in mice are dependent on age.
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.
Sternberg
Wendy F
WF
Department of Psychology, Haverford College, 370 Lancaster Avenue, Haverford, PA 19041, USA. wsternbe@haverford.edu
Ritchie
Jennifer
J
Mogil
Jeffrey S
JS
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology; D030762:Estrous Cycle / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D008593:Menopause / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism; D012727:Sex Characteristics
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D012739:Gonadal Steroid Hormones; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer