Evidence for Effects on Neurology and Behavior - BioInitiative Report

times that of chlordiazepoxide [Braestrup and Squires, 1978; Mohler and Okada, 1977]. The
ranges of diazepam and chlordiazepoxide used in the Thomas studies [Thomas et al., 1979,
1980] were 0.5-20 and 1-40 mg/kg, respectively. Thus, the doses of diazepam studied might be
equivalent or higher in potency than the highest dose of chlordiazepoxide used. This supposition
was supported by the observation in the Thomas studies that the effects of the two drugs were
different. The dose-response curve of chlordiazepoxide on the DRL-schedule operant responses
showed a dose-dependent inverted-U function, i.e., potentiation at medium dose, attenuation at
higher dose, and only the portion of the response-curve that showed potentiation was affected by
RFR [Thomas et al., 1979]. In the study of Thomas et al. [1980] on diazepam, only attenuation of
DRL-responses was observed. Thus, the dose range of diazepam used in the study was at the
attenuation portion of the dose-response function, which is not affected by RFR. These dosedependent
potentiation and attenuation effects of benzodiazepines on the operant response may
involve different neural mechanisms. Radiofrequency radiation may only affect and enhance the
potentiating and not the attenuating effect of benzodiazepines, which is possible because our
research [Lai et al., 1992a] showed that the effect of RFR on benzodiazepine receptors is brainregion
selective. Thus, the data of Thomas et al. [1979, 1980] on the interaction of RFR
irradiation on benzodiazepine actions could be explained by a selective increase in
benzodiazepine receptors in different regions of the brain. Another possibility is that RFR affects
only the subtype of benzodiazepine receptors related to antianxiety effect and not another
subtype related to the sedative-hypnotic action of the drugs. In the dose-response curve of
benzodiazepine on DRL-schedule maintained behavior, the potentiation portion may be due to
the <strong>for</strong>mer receptor subtypes and the attenuation portion the latter subtype. There is ample
evidence suggesting that different subtypes of benzodiazepine receptors subserve antianxiety and
sedative effects [Polc, 1988].
In addition to the above studies on the effect of RFR on benzodiazepines, Monahan and
Henton [1979] trained mice to avoid or escape from 2450-MHz RFR (45 W/kg) under an
avoidance paradigm. They reported that pretreatment of the animals with chlordiazepoxide
decreased the avoidance response and increased the escape responses, which led to an increase in
the animal's cumulative exposure to RFR after the drug treatment. The authors speculated that
RFR potentiated the effect of chlordiazepoxide and caused a decrement in the avoidance
response. It is also interesting that in the procedure the presence of RFR was signalled
simultaneously with a tone and the animal could elicit an avoidance response, which resets the
timer and delays the further presentation of RFR. Thus, the procedure had both signalled and
continuous avoidance components. However, the data indicate that the effect was more like a
continuous avoidance paradigm. Generally, anxiolyltic agents like benzodiazepines decrease
both avoidance and escape behavior in a signalled-avoidance paradigm, but they can selectively
decrease the avoidance response and leave the escape responding intact under a continuous
avoidance paradigm.
Johnson et al. [1980] reported that repeated exposure (twenty-one 45-min sessions) to RFR
(2450 MHz, pulsed, average whole body SAR 0.6 W/kg) reduced the sedative hypnotic effect,
but increased the feeding behavior induced by diazepam. Hjeresen et al. [1987] reported that the
attenuation effect of a single (45 min) RFR exposure (2450 MHz, CW, average whole body SAR
0.3 W/kg) on ethanol-induced hypothermia was blocked by treating the rat with the
benzodiazepine antagonist, RO 15-1778. The data indicated that benzodiazepine receptors in the
brain might mediate the effects of RFR on ethanol-hypothermia. In a more recent study, Quock
et al. [1990] investigated the influence of RFR exposure on the effect of chlordiazepoxide on the
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