Sex differences in the inhibitory effects of the NMDA antagonist, MK-801, on morphine and stress-induced analgesia.
We examined the effects of intraperitoneal administrations of the noncompetitive NMDA receptor antagonist, (+) MK-801, its inactive enantiomer, (-) MK-801, and the prototypic opiate antagonist, naloxone, on restraint- and morphine-induced analgesia in male and female deer mice, Peromyscus maniculatus. Both restraint (30 min) and morphine (1.0 mg/kg) induced significant analgesic responses with male mice displaying significantly greater levels of opioid-induced analgesia than female animals. These analgesic responses were completely blocked by, naloxone (1.0 mg/kg), significantly reduced by (+) MK-801 (0.25 mg/kg) and unaffected by (-) MK-801 (0.25 mg/kg) pretreatments. There were significant male-female differences in the inhibitory effects of (+) MK-801; the higher levels of morphine- and restraint-induced analgesia of the males were completely blocked, while the lower level analgesic responses of the females were significantly reduced, but not blocked, by (+) MK-801. These observations provide further evidence that NMDA receptors are involved in the mediation of endogenous and exogenous opioid analgesia and show that there are significant male-female differences in the inhibitory effects of (+) MK-801 on opioid-mediated analgesia.
Lipa
S M
SM
Division of Oral Biology, Faculty of Dentistry, University of Western Ontario, London, Canada.
Kavaliers
M
M
D000698:Analgesia; D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010542:Peromyscus; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012149:Restraint, Physical; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000503:physiopathology*
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D009270:Naloxone; D016291:Dizocilpine Maleate; D009020:Morphine