Sex and genotype determine the selective activation of neurochemically-distinct mechanisms of swim stress-induced analgesia

Pharmacology, Biochemistry, and Behavior
Jeffrey S Mogil, J K Belknap

Abstract

A growing literature documents the important influence of organismic factors such as sex and genotype on pain sensitivity and pain modulation. We recently determined that 3-min forced swims in 15 degrees C water produce non-opioid (i.e., naloxone-insensitive) analgesia in outbred Swiss-Webster mice of both sexes; this form of stress-induced analgesia (SIA) is significantly attenuated by the N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801) in males, but not females. A pilot study designed to confirm the non-opioid and (in male mice) NMDAergic nature of 15 degrees C swim SIA in the C57BL/6J and DBA/2J inbred strains used widely in gene mapping was conducted, using the hot-plate (54 degrees C) assay of nociception. In female mice of both strains, 15 degrees C swim SIA was insensitive to antagonism by either naloxone (10 mg/kg, i.p.) or dizocilpine (0.1 mg/kg. i.p.). In male C57BL/ 6J mice, the observed SIA was naloxone-insensitive, but was attenuated by dizocilpine. This pattern of results is virtually identical to that obtained using Swiss-Webster mice in this and previous studies. However, male DBA/2J mice displayed SIA that was significantly attenuated by naloxone, but insensitive to dizocilpine antagonism. These fi...Continue Reading

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