Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement.
Sex differences in the neurochemical mediation of swim stress-induced analgesia (SSIA) were examined in Swiss-Webster mice. Intact and gonadectomized adult mice of both sexes were tested for their analgesic response (hot-plate test) to 3 min of forced swimming in 15 degrees C and 20 degrees C water. SSIA resulting from 15 degrees C swim was previously shown to be naloxone-insensitive (i.e., non-opioid) whereas SSIA resulting from 20 degrees C swim produced an analgesia that was partially reversible by naloxone (i.e., mixed opioid/non-opioid). The non-opioid components of these SSIA paradigms were attenuated by the N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801). We now report that in males, but not females, dizocilpine (0.075 mg/kg, i.p.) and naloxone (10 mg/kg, i.p.) antagonized the non-opioid and opioid components of SSIA, respectively. After ovariectomy, females displayed a pattern of antagonism similar to males such that dizocilpine attenuated non-opioid SSIA, although naloxone remained ineffective in antagonizing 20 degrees C SSIA. Thus, SSIA in intact females was neither opioid- nor NMDA-mediated, yet it was of similar magnitude to the SSIA displayed by intact males. In separate experiments, estrogen replacement (estrogen benzoate; 5.0 micrograms/day, i.p.) administered to ovariectomized mice over a 6-8 day period reinstated the dizocilpine-insensitivity of 15 degrees C SSIA characteristic of intact females. However, a similar estrogen regimen administered to both intact and castrated males did not compromise the sensitivity to dizocilpine previously noted in male mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Mogil
Jeffrey S
JS
Department of Psychology and Brain Research Institute, University of California at Los Angeles, Los Angeles, CA 90024 USA.
Sternberg
Wendy F
WF
Kest
Benjamin
B
Marek
Przemyslaw
P
Liebeskind
John C
JC
D000698:Analgesia; D000818:Animals; D001835:Body Weight; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009919:Orchiectomy; D010052:Ovariectomy; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000523:psychology*; D013550:Swimming
D004967:Estrogens; D009270:Naloxone; D016291:Dizocilpine Maleate