Acute progesterone can recruit sex-specific neurochemical mechanisms mediating swim stress-induced and kappa-opioid analgesia in mice.
There is a qualitative sex difference in the neurochemical mediation of stress-induced and kappa-opioid analgesia; these phenomena are dependent on N-methyl-d-aspartic acid (NMDA) receptors in males but not females. Progesterone modulation of this sex difference was examined in mice. Analgesia against thermal nociception was produced by forced cold water swim or by systemic administration of the kappa-opioid agonist, U50,488. As seen previously, the NMDA receptor antagonist MK-801 blocked both forms of analgesia in male but not female mice. Also as in previous studies, this sex difference was found to be dependent on ovarian hormones such that ovariectomy induced female mice to "switch" to the male-like, NMDAergic system. We now demonstrate that a single injection of progesterone (50 microg), systemically administered 30 min before analgesia assessment, is sufficient to restore female-specific mediation of analgesia (i.e., insensitivity to MK-801 blockade) in ovariectomized female mice. The rapidity of this neurochemical "switching" action of progesterone suggests mediation via cell surface receptors or the action of neuroactive steroid metabolites of progesterone.
Department of Psychology, Haverford College, Haverford, PA 19041, USA. wsternbe@haverford.edu
Wendy F
WF
Sternberg
Elissa J
EJ
Chesler
Sonya G
SG
Wilson
Jeffrey S
JS
Mogil
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002369:Castration; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D010052:Ovariectomy; D010146:Pain / Q000503:physiopathology*; D011374:Progesterone / Q000008:administration & dosage / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming / Q000523:psychology
D018712:Analgesics, Non-Narcotic; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D011374:Progesterone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D016291:Dizocilpine Maleate