N-METHYL-D-ASPARTIC ACID (NMDA) RECEPTOR ANTAGONIST MK-801 BLOCKS NONOPIOID STRESS-INDUCED ANALGESIA .2. COMPARISON ACROSS 3 SWIM-STRESS PARADIGMS IN SELECTIVELY BRED MICE

The effects of the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (dizocilpine, 0.075 mg/kg, i.p.) on swim-stress-induced analgesia (SSIA) were studied in control (C) mice and in mice selectively bred for high (HA) or low (LA) SSIA. In three consecutive experiments, animals were subjected to forced swimming at water temperatures of 20-degrees-C, 32-degrees-C and 15-degrees-C and the resulting analgesia (hot-plate test) was found to be mixed opioid/non-opioid, opioid and non-opioid, respectively, as a function of the degree of antagonism by naloxone (10 mg/kg, i.p.). The major finding of this study is that MK-801 attenuated 15-degrees-C SSIA, against which naloxone was ineffective, but had no effect on 32-degrees-C SSIA, which naloxone blocked completely. A combination of naloxone and MK-801 significantly attenuated 20-degrees-C SSIA in C and HA mice and in HA mice this attenuation was significantly larger than that produced by either drug alone. Morphine analgesia (10 mg/kg, i.p.) was unaffected by MK-801. It is concluded that low doses of MK-801 selectively block non-opioid mechanisms of SSIA.