Evidence for Effects on Neurology and Behavior - BioInitiative Report

stair-case test <strong>for</strong> mouse, a test <strong>for</strong> both the sedative and antianxiety effects of benzodiazepines.
They reported that acute exposure (5 min at a whole body average SAR of 36 W/kg) caused a
significant reduction of the sedative, but not the antianxiety effect of chlordiazepoxide. The
effect was probably related to hyperthermia. Some of the above effects of RFR on
benzodiazepine actions can be explained by our finding [Lai et al., 1992a] that acute RFR
exposure increased benzodiazepine receptors in selective regions of the brain and that adaptation
occurred after repeated exposure.
On the other hand, central benzodiazepine receptors can also affect seizure susceptibility in
animals. Benzodiazepines are widely used as anticonvulsants. Exposure to RFR has been shown
to affect seizure and convulsion susceptibility in animals. For example, Stverak et al. [1974]
reported that chronic exposure to pulsed RFR attenuated audiogenic seizures in seizure-sensitive
rats. Servantie et al. [1974] showed that mice chronically exposed to pulsed RFR initially
showed a decrease and then an increase in susceptibility to the convulsant pentylenetetrazol.
However, Pappas et al. [1983] showed no significant interaction effect of RFR on
pentylenetetrazol-induced seizures nor the efficacy of chlordiazepoxide to block the seizure in
rats. A more thorough study of the different parameters of RFR exposure on benzodiazepine
receptors in the brain may explain these findings. Benzodiazepine receptors are very dynamic
and can undergo rapid changes in properties in response to environmental stimuli [Braestrup et
al., 1979; Lai and Carino, 1990b; Medina et al., 1983a,b; Soubrie et al., 1980; Weizman et al.,
1989]. However, the direction of change and extent of effect depend on the stimulus and
experimental conditions.
We conducted experiments to study the effect of acute RFR exposure on the actions of
various psychoactive drugs [Lai et al., 1983; 1984a,b]. We found that acute (45 min) exposure to
pulsed 2450-MHz RFR (2 s pulses, 500 pps, 1 mW/cm 2 , whole body average SAR 0.6 W/kg)
enhanced apomorphine-hypothermia and stereotypy, morphine-catalepsy, and pentobarbitalhypothermia
and narcosis, but it attenuated amphetamine-hyperthermia and ethanol-hypothermia.
These psychoactive drugs are lipid-soluble and readily enter the central nervous system and the
effects observed are not unidirectional, i.e., depending on the drug studied, increase or decrease
in action was observed after RFR exposure. There<strong>for</strong>e, these effects cannot be explained as a
change in entry of the drugs into the brain, e.g., change in blood-brain barrier permeability or
alteration in drug metabolism as a result of RFR exposure. Our finding that acute low-level RFR
attenuated ethanol-hypothermia in the rat was replicated by Hjeresen et al. [1988] at a lower
whole body average SAR of 0.3 W/kg. Blood ethanol level measurements indicated that the
effect was not due to changes in metabolism or disposition of ethanol in the body. Results from
further experiments [Hjeresen et al., 1989] suggested that the -adrenergic mechanism in the
brain might be involved in the attenuation effect of RFR on ethanol-induced hypothermia in the
rat.
We further found that the effects of RFR on amphetamine-hyperthermia [Lai et al., 1986b]
and ethanol-hypothermia could be classically conditioned to cues in the exposure environment
after repeated exposure. Another interesting finding in our research was that some of the effects
of RFR on the actions of the psychoactive drugs could be blocked by pretreating the rats with
narcotic antagonists be<strong>for</strong>e exposure, suggesting the involvement of endogenous opioids [Lai et
al., 1986b]. The hypothesis that low-level RFR activates endogenous opioids in the brain was
further supported by an experiment showing that the withdrawal syndromes in morphinedependent
rats could be attenuated by RFR exposure [Lai et al., 1986a]. This hypothesis can
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