THERMAL TOLERANCE REDUCES HYPERTHERMIA-INDUCED DISRUPTION OF WORKING-MEMORY - A ROLE FOR ENDOGENOUS OPIATES

Previous reports indicate that microwave-induced hyperthermia can impa ir learning and memory. Here, we report that preexposure to a single 2 0-min period of hyperthermia can produce thermal tolerance and, thereb y, attenuate future physiological and behavioral reactions to heating. Because endogenous opioids have been implicated in thermoregulation a nd reactions to microwave exposure, we also determined how opioid rece ptor antagonism might modulate these effects. In an initial experiment , rats were exposed daily, over 5 successive days, to 600-MHz microwav es (at a whole-body specific absorption rate of 9.3 W/kg) or sham expo sed. In animals exposed to microwaves, thermal tolerance was evidenced by declining rectal temperatures over time. Temperature reductions fo llowing microwave exposure were prominent after a single previous expo sure. Therefore, in a second study, a single hyperthermic episode was used to induce thermal tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. Just prior to radiation/ sham-radiation treatment, rats received either saline or naltrexone (0 .1 or 10 mg/kg, intraperitoneally (i.p.)). The following day (Day 2), rats were either microwave or sham exposed and tested on a task which measures the relative time subjects explore a familiar versus a novel stimulus object. Normothermic rats spend significantly more time in co ntact with new environmental components and less time with familiar ob jects. Brain (dura) and rectal temperatures were recorded on both days of the study. Microwave exposure produced a reliable hyperthermia whi ch was significantly lower (on Day 2) in rats receiving repeated treat ments (tolerant group). On the behavioral test, rats exposed only once to microwave-induced hyperthermia (nontolerant group) exhibited signi ficantly different patterns of object discrimination than did tolerant or sham-exposed animals. Sham-exposed and tolerant animals showed a d istinct preference for the new object whereas the nontolerant animals did not. Naltrexone (10 mg/kg) antagonized the hyperthermia-induced di sruption of the object discrimination task; (in nontolerant rats) and produced patterns of object exploration that were similar to those of sham-irradiated and thermal-tolerant rats, suggesting that endogenous opioids play a role in the organism's response to heating. Taken toget her, these data are consistent with the conclusions that 1) microwave- induced hyperthermia can cause a dose-dependent disruption of the norm al discrimination between new and familiar objects, 2) physiological r eactions to a single hyperthermic episode can produce a thermotoleranc e that expresses itself in both reduced levels of hyperthermia and att enuated behavioral disruptions following microwave exposure, and 3) op ioid antagonism can partially reverse some of the behavioral effects o f microwave-induced hyperthermia. (C) 1998 Elsevier Science Inc.