Neonatal testosterone exposure influences neurochemistry of non-opioid swim stress-induced analgesia in adult mice

Pain. 1995 Dec;63(3):321-326. doi: 10.1016/0304-3959(95)00059-3.


The effects of neonatal hormone manipulations on swim stress-induced analgesia (SSIA) magnitude and neurochemical quality were examined in Swiss-Webster mice of both sexes. Previous research has indicated that non-opioid SSIA mechanisms in adult Swiss-Webster mice are sexually dimorphic. Male mice exhibit non-opioid SSIA following a 3-min swim in cold (15 degrees C) water that is antagonized by the non-competitive NMDA antagonist MK-801 (dizocilpine; 0.075 mg/kg), whereas female mice do not display NMDA-mediated analgesia in the presence of estrogen. Since male and female mice show equipotent magnitudes of SSIA, it was concluded that female mice display a neurochemically distinct, estrogen-dependent SSIA mechanism specific to their gender. In the present study, female mice exposed to testosterone during the neonatal period display NMDA-mediated analgesia even in the presence of estrogen in adulthood. Thus, expression of the female-specific, estrogen-dependent SSIA mechanism previously described may be dependent on the absence of testosterone during early ontogeny.

Publication types

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

MeSH terms

  • Analgesia*
  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Body Weight / physiology
  • Brain / embryology*
  • Dizocilpine Maleate / pharmacology
  • Estrogens / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Male
  • Mice
  • Orchiectomy
  • Pain Measurement / drug effects
  • Pregnancy
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Sex Characteristics
  • Stress, Psychological / physiopathology*
  • Swimming
  • Testosterone / pharmacology*


  • Estrogens
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Testosterone
  • Dizocilpine Maleate