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PubMed1993

Chlordiazepoxide block of two types of calcium channels in neuroblastoma cells.

Chlordiazepoxide is a benzodiazepine that is widely used as a minor tranquilizer. It is also effective in the treatment of acute alcohol withdrawal. In this setting, chlordiazepoxide acts as a sedative and prevents the development of epileptiform activity. Although benzodiazepines are known to augment gamma-aminobutyric acid-activated chloride channels, an action which at least partially accounts for their anticonvulsant properties, there is some evidence to suggest that voltage-activated calcium channels may also be the target of these agents. We therefore studied the effect of chlordiazepoxide in blocking two distinct types of voltage-activated calcium channels in N1E-115 neuroblastoma cells. Chlordiazepoxide reversibly blocked calcium channels in both closed and open configurations. It was slightly more potent in blocking the transient (T-type or type I) than the long-lasting (L-type or type II) type of calcium channels with apparent Ki values of 311 and 398 microM, respectively. In the presence of chlordiazepoxide, the currents of both types of calcium channel currents decayed more quickly than control, an observation that suggests open channel block. Chlordiazepoxide-induced block of T-type calcium channels was use dependent, increasing with an increase in stimulus frequency. This was due primarily to the acceleration of current decay and slowing of recovery from inactivation by chlordiazepoxide. These calcium channel blocking actions could contribute some to the sedative and anticonvulsant properties of chlordiazepoxide in patients suffering from acute alcohol withdrawal and in electric shock-induced seizures in animal models.

Animals↗

PubMed1999

Naltrexone potentiates the anxiolytic effects of chlordiazepoxide in rats exposed to novel environments.

RATIONALE: Both novelty and naloxone have been reported to modify the anxiolytic-like effect of benzodiazepines in the elevated plus maze. In addition, it has been largely demonstrated that novelty alters endogenous opioid activity. OBJECTIVES: The present study was designed to examine a possible interaction between novelty and naltrexone effects on the behavior of chlordiazepoxide-treated rats in two animal models of anxiety. METHODS: Thirty minutes after acute intraperitoneal treatment with saline or naltrexone and saline or chlordiazepoxide, male Wistar rats were exposed for the first time to the elevated plus maze apparatus or the social interaction arena for the quantification of the percentage of time spent in the open arms or the time of active social interaction, respectively. The effects of naltrexone and/or chlordiazepoxide on the plus maze and the social interaction tests were also evaluated after previous exposure to the respective apparatus. RESULTS: Naltrexone dose dependently increased the percentage of time spent in the open arms of the elevated plus maze in chlordiazepoxide-treated (5 mg/kg i.p.) rats exposed for the first time to the apparatus. Similarly, naltrexone (5 mg/kg i.p.) increased the time spent in active social interaction by chlordiazepoxide-treated rats exposed to an unfamiliar arena. In both experiments, naltrexone had no effect when administered alone. When both the plus maze and the social interaction tests were conducted after previous exposure to the respective apparatus, naltrexone did not modify the behavior of chlordiazepoxide- or saline-treated rats. CONCLUSIONS: These data suggest that the anxiolytic-like effects of chlordiazepoxide can be modified by opioid mechanisms in novel environments.

Animals↗

PubMed1981

The effects of chlordiazepoxide on synaptic transmission and amino acid neurotransmitter release in slices of rat olfactory cortex.

The rat olfactory cortex slice has been used to investigate the effects of chlordiazepoxide on evoked field potentials and the release of endogenous amino acid neurotransmitters (aspartate, glutamate, GABA and possibly taurine) which accompany electrical stimulation of the lateral olfactory tract. When single, low frequency stimuli were employed, chlordiazepoxide (2 microM-1 mM) depressed the amplitude of the field potential correlate of the depolarizing actions of the lateral olfactory tract excitatory transmitter (aspartate?) although aspartate release was unaffected. The field potential correlate of GABA-mediated presynaptic inhibition (late N-wave) was also depressed in amplitude but low drug concentrations (between approximately 2 and 50 microM) increased its peak duration . Effects of chlordiazepoxide on evoked inhibition were analyzed by giving paired stimuli such that the second stimulus occurred during the field potentials evoked by the first stimulus. Chlordiazepoxide (1-20 microM) increased the depression in amplitudes of the presynaptic massed action potential and late N-wave evoked by the second of a pair of stimuli compared with those evoked by the first stimulus suggesting that presynaptic inhibition was potentiated. These effects of chlordiazepoxide were accompanied by a significant reduction in aspartate release from the lateral olfactory tract terminals. Moreover, the drug effects on presynaptic inhibition and aspartate release were antagonized by picrotoxin (5 microM). On the other hand, chlordiazepoxide (1-50 microM) had no significant effect on postsynaptic inhibition. The results are discussed in terms of both the sites (presynaptic or postsynaptic) and mechanisms of action of chlordiazepoxide.

4-Aminobutyrate Transaminase↗

PubMed1993

A phase-response curve to the benzodiazepine chlordiazepoxide and the effect of geniculo-hypothalamic tract ablation.

The geniculo-hypothalamic tract (GHT) provides input to the mammalian circadian pacemaker in the suprachiasmatic nucleus. Several recent reports indicate that GHT ablation blocks phase shifts to the benzodiazepines triazolam and chlordiazepoxide at circadian times (CTs) 6 and 21. In this study we tested if GHT ablation blocks phase shifts to chlordiazepoxide at a wide range of circadian phases. Syrian hamsters were housed under constant dim light, and running-wheel activity rhythms were monitored. Intraperitoneal injections of either chlordiazepoxide (100 mg/kg) or saline were administered at various circadian times, and a phase-response curve was constructed. In intact animals, chlordiazepoxide produced phase-advance shifts at CTs 0, 4, 6, and 8, and phase-delay shifts between CTs 12-14. Although bursts of increased activity were sometimes observed on the day of injection, activity does not appear to mediate chlordiazepoxide-induced phase shifts. Hamsters with > 45% GHT ablation showed no phase shifts > 20 min to chlordiazepoxide. Our results indicate that the geniculo-hypothalamic tract is necessary for the phase-shifting effects of the benzodiazepine chlordiazepoxide throughout the circadian cycle.

Animals↗

PubMed1980

Effects of chlordiazepoxide, food familiarization, and prior shock experience on food choice in rats.

Chlordiazepoxide (5, 10 mg/kg) increased the time devoted to eating familiar laboratory chow without altering the response to a range of novel, palatable foods which were also available to the food-deprived rats. Prior experience with the same range of alternative foods (food familiarization) radically changed the effect of the drug. After familiarization with these foods, chow was virtually ignored as a food choice, indicating its low relative palatability; chlordiazepoxide then prolonged the time eating the familiarized foods without significantly increasing the response to chow. These results are not consistent with an anti-food neophobia action of chordiazepoxide. They suggest instead that chlordiazepoxide enhances feeding responses related to food saliency. Footshock, delivered two days before the food choice test affected performance within the test. Its effects were opposite those of chlordiazepoxide, but they competed additively with the drug's effects. These results indicate that chlordiazepoxide's action was not simply to remove any inhibitory effect on feeding produced by fear; instead the drug promoted approach to food antagonizing any deficit in approach associated with fear. These findings are viewed as consistent with an action of chlordiazepoxide to augment the level of feeding motivation. Chlordiazepoxide (15 mg/kg) may act to overcome food neophobia.

Animals↗

PubMed1989

Pituitary thyrotropin-releasing hormone (TRH) receptors: effects of TRH, drugs mimicking TRH action, and chlordiazepoxide.

Binding of TRH to specific cell surface receptors on clonal GH4C1 cells is followed within 10 min by receptor sequestration and over 24 h by receptor down-regulation. These experiments were designed to determine if TRH-activated second messenger systems are responsible for changes in receptor localization or number. BAY K8644 and A23187, which increase intracellular calcium, alone or together with 12-O-tetradecanoyl phorbol acetate (TPA), which activates protein kinase C, did not appear to internalize TRH receptors. Drug treatment did not alter the rate of [3H]MeTRH association or internalization, determined by resistance to an acid/salt wash, or the amount of [3H]MeTRH able to bind at 0 C, where only surface receptors are accessible. TPA (0-100 nM) alone or in combination with BAY K8644 or A23187, also failed to change receptor number or affinity after 48 h when TRH caused a 75% decrease in the density of specific binding sites. Chlordiazepoxide has been reported antagonize TRH binding and TRH-induced phospholipid breakdown. Chlordiazepoxide shifted the dose-response curves for TRH stimulation of PRL release and synthesis to the right, and did not change PRL release alone. The affinity of receptors for chlordiazepoxide was not affected by a nonhydrolyzable analog of GTP whereas affinity for TRH was decreased; these properties are consistent with the classification of chlordiazepoxide as a competitive antagonist. Several experiments tested whether chlordiazepoxide would cause receptor internalization and down-regulation. Chlordiazepoxide did not appear to internalize TRH receptors, because TRH-binding sites became available rapidly and at the same rate after they had been saturated with chlordiazepoxide at 0 or 37 C.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMedDate not supplied

Clinical pharmacokinetics of chlordiazepoxide.

Chlordiazepoxide was the first benzodiazepine derivative made available for clinical use. The metabolic pathway of chlordiazepoxide is complex, since the drug is biotransformed into a succession of pharmacologically active products: desmethylchlordiazepoxide, demoxepam, desmethyldiazepam, and oxazepam. The elimination half-life (tl/2beta) of chlordiazepoxide following single doses, in healthy individuals generally ranges from 5 to 30 hours, and the volume of distribution from 0.25 to 0.50 liters/kg. The hepatic extraction ratio is well under 5%. Elimination of the parent compound is mirrored by formation of the first active metabolite. Clearance of chlordiazepoxide is reduced and tl/2beta is prolonged in the elderly, in those with cirrhosis, and in those receiving concurrent disulfiram therapy. Oral chlordiazepoxide is rapidly and completely absorbed, but intramuscular injection is painful and results in slow and erratic absorption. Multiple-dose therapy with chlordiazepoxide results in accumulation of the parent compound, as well as two or more of its active metabolites. The rate and extent of accumulation varies considerably between individuals. A relation between plasma concentrations of chlordiazepoxide and its metabolites to clinical effects has been suggested in some studies and is currently under further investigation.

Administration, Oral↗

PubMed1983

Chlordiazepoxide reduces in vivo serotonin release in the basal ganglia of encéphale isolé but not anesthetized cats: evidence for a dorsal raphe site of action.

By using a push-pull cannula technique and an isotopic method for the estimation of [3H]serotonin continuously synthetized from [3H]tryptophan, the effects of a benzodiazepine, chlordiazepoxide, were investigated on the in vivo release of [3H]serotonin in the cat basal ganglia. Chlordiazepoxide injection (10 mg/kg i.p.) decreased striatal and nigral [3H]serotonin release and enhanced the [3H]amine release in the dorsal raphe. These changes were blocked by the continuous superfusion of the dorsal raphe with Ro 15-1788 (10(-5) M), a benzodiazepine receptor antagonist. Chlordiazepoxide (10(-5) M) applied to the dorsal raphe reduced nigral [3H]serotonin release while decreasing [3H]serotonin release locally in the dorsal raphe. Furthermore, the superfusion of serotonergic nerve terminals of the substantia nigra or the caudate nucleus with chlordiazepoxide (10(-5) M) never altered the local release of [3H]serotonin. These data strongly suggest that the (inhibitory) influences exerted by chlordiazepoxide on serotonergic transmission more likely involved cell bodies and/or dendrites rather than terminals of serotonergic neurons. Chlordiazepoxide-induced changes in [3H]serotonin release were only observed in "encéphale isolé" and not in halothane-anesthetized cats. Further experiments revealed that GABAergic neurons of the dorsal raphe could participate to such a differential reactivity of serotonergic cells to chlordiazepoxide. For instance, [3H]gamma-aminobutyric acid release in the dorsal raphe was enhanced by halothane anesthesia. These findings further suggest the possibility that the influence exerted by benzodiazepines on serotonergic transmission, perhaps through a gamma-aminobutyric acid-dependent process, can significantly be involved in the pharmacological actions of these drugs.

Anesthesia↗

PubMed1976

Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption.

Ten healthy male subjects ingested 25 mg of chlordiazepoxide hydrochloride (Librium) with 100 ml of water or with 100 ml of magnesium and aluminum hydroxide (Maalox) in a single-dose crossover study. Multiple venous blood samples drawn during the first 24 hr after each dose were assayed for concentrations of chlordiazepoxide and its major metabolite, desmethylchlordiazepoxide. The antacid prolonged the mean chlordiazepoxide absorption half-time from 11 to 24 min, and in 6 of 10 subjects delayed achievement of the peak blood concentration by from 0.5 to 3.0 hrs. The formation of desmethylclordiazepoxide was also slowed. The areas under the 24 hr blood concentration curve for chlordiazepoxide and for its metabolite were not influenced by the antacid. The apparent elimination half-life of chlordiazepoxide (8.4 and 8.2 hr) was not significantly affected. Administration of chlordiazepoxide with antacid reduces the rate of its absorption but does not alter the completeness of absorption or the apparent rate of elimination.

Adult↗

PubMed1975

Radioimmunoassay of chlordiazepoxide in plasma.

A simple, rapid, and sensitive radioimmunoassay was developed for the determination of chlordiazepoxide (7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide) in plasma. Antiserum capable of binding chlordiazepoxide-2-14C was obtained from rabbits following immunization with an antigen prepared by coupling the reactive acyl azide of 7-chloro-5-(4-hydrazinocarbonylmethoxyphenyl)-2-methylamino-3H-1,4-benzodiazepine 4-oxide to bovine serum albumin. The radioimmunoassay allows for the specific determination of chlordiazepoxide directly in plasma without extraction and was compared with a differential spectrofluorometric assay for chlordiazepoxide. Both methods gave satisfactory agreement for the plasma levels of chlordiazepoxide in human subjects resulting from single and chronic oral doses of chlordiazepoxide hydrochloride.

Administration, Oral↗

PubMed1986

Effects of training dose on discrimination and cross-generalization of chlordiazepoxide, pentobarbital and ethanol in the rat.

Six groups of rats (N = 8), trained to discriminate chlordiazepoxide (5 or 20 mg/kg), pentobarbital (5 or 15 mg/kg) or ethanol (750 or 1500 mg/kg) from saline in a two-lever food-reinforced procedure, were tested for stimulus generalization with the three drugs. Training drug, but not training dose, affected the extent of generalization to a test drug; symmetrical generalization between chlordiazepoxide and pentobarbital and asymmetrical generalization between chlordiazepoxide and ethanol and between pentobarbital and ethanol was observed. Training dose level affected slope and ED50 of the generalization gradients of training drugs and substitution drugs, discriminative performance, response bias and threshold dose for response suppression. Indices of lever selection and percentage drug-appropriate lever responses yielded similar generalization maxima, slopes and ED50S. The potency of chlordiazepoxide relative to the potency of pentobarbital to induce drug stimulus generalization varied across the experimental groups. The results indicate differences between the discriminative effects of chlordiazepoxide, pentobarbital and ethanol. It is suggested that the discriminative effects of chlordiazepoxide, pentobarbital and ethanol are not based on their response rate modulating effects and that training dose is not a determinant for the extent of cross-generalization between these compounds.

Animals↗

PubMed1985

The sedative effects of CL 218,872, like those of chlordiazepoxide, are reversed by benzodiazepine antagonists.

The effects of CL 218,872, initially classified as a non-sedative anxiolytic, were investigated and compared with those of chlordiazepoxide in the holeboard. The ability of two drugs that antagonise the effects of benzodiazepines, CGS 8216 and Ro 15-1788, to reverse the effects of CL 218,872 and chlordiazepoxide were also investigated, to see whether their effects might be mediated via benzodiazepine receptors. CL 218,872 (10 mg/kg) was found to be significantly sedative in both mice and rats (i.e., both locomotor activity and head-dipping were significantly decreased). In mice, the effects of CL 218,872 and of chlordiazepoxide were very similar over a range of doses, except that the stimulatory effect seen with low doses of chlordiazepoxide on head-dipping just failed to reach significance with CL 218,872. This study is in agreement with recently published results from different tests showing that sedative effects can be obtained with doses of CL 218,872 that are low and not much higher than those leading to anxiolysis. The sedative effects of both CL 218,872 (10 mg/kg) and chlordiazepoxide (20 mg/kg) were significantly reversed by RO 15-1788 (10 and 20 mg/kg) and CGS 8216 (10 mg/kg), suggesting that their effects are mediated via benzodiazepine receptors. The increase in head-dipping seen with chlordiazepoxide (2.5 mg/kg) was also reversed by RO 15-1788 and CGS 8216.

Animals↗

PubMed1980

Short-term ethanol administration impairs the elimination of chlordiazepoxide (Librium) in man.

Ethanol may enhance the sedative effect of benzodiazepines leading to greater psychomotor impairment, but the mechanism is not clear. The present study was carried out to determine the effect of acute ethanol ingestion on the disposition and elimination of chlordiazepoxide (Librium), a widely used benzodiazepine. Five healthy, 22-39-year-old, male volunteers ingested ethanol 0.8 g/kg as 25% in orange juice 1 h before chlordiazepoxide 0.6 mg/kg was injected intravenously. To maintain plasma ethanol concentrations of 50-150 mg!100 ml for 32 h additional ethanol 0.5 g/kg was given orally every 5 h. Plasma clearance of chlordiazepoxide fell from 26.6 +/- 2.6 ml/min (mean +/- SD) without ethanol to 16.6 +/- 3.1 ml/min (P less than 0.05) after ethanol. There was no change in the volume of distribution and therefore the elimination half-life was prolonged from 7.1 +/- 1.9 h to 11.8 +/- 6.0 h (P less than 0.05) after ethanol. Ethanol also lowered the plasma binding of chlordiazepoxide from 94.7 +/- 0.6% to 93.4 +/- 1.3% (P less than 0.05). The plasma clearance of unbound chlordiazepoxide fell from 468 +/- 51 ml/min to 264 +/- 98 ml/min (P less than 0.05) after ethanol. The plasma level of the metabolite desmethylchlordiazepoxide was higher and its elimination slower after ethanol. Thus using a pharmacokinetic approach this study has demonstrated that short-term ethanol ingestion in moderate doses impairs the elimination of chlordiazepoxide and accounts, at least partly, for the greater sedation that results when ethanol is taken concomitantly.

Adult↗

PubMed1999

Differential EEG effects of the anxiolytic drugs, deramciclane (EGIS-3886), ritanserin and chlordiazepoxide in rats.

The influence of serotonergic and benzodiazepine type anxiolytic drugs on the cortical activation and sleep-wakefulness cycle were compared by evaluating the effects of ritanserin and deramciclane (EGIS-3886), two 5-HT2 receptor antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all drugs), EEG was continuously sampled for 6 h and power spectra were calculated for every 5 s to assess changes in slow wave activity and sleep phases. In a separate test, anticonvulsant effects of the drugs were examined in mice. Both deramciclane and ritanserin slightly increased total time spent in deep sleep (DS) and lengthened sleep episodes. In contrast, chlordiazepoxide had a strong inhibitory action on DS, sleep time being shifted to more superficial light sleep (LS). The incidence and length of the high voltage spindle (HVS) episodes characteristic for the motionless, awake rat were increased at the highest dose of both deramciclane and ritanserin, while it was decreased by chlordiazepoxide. In mice, chlordiazepoxide had a marked anticonvulsant effect, while deramciclane was moderately effective and ritanserin ineffective. In conclusion, the 5-HT2 receptor antagonist anxiolytic drugs seem to be superior compared to the benzodiazepine type anxiolytic drug, chlordiazepoxide, as ritanserin and deramciclane improved sleep quality by increasing sleep episode length and time spent in DS, while chlordiazepoxide enhanced sleep fragmentation and decreased DS.

Analysis of Variance↗

PubMed1982

Effects of opiate antagonists and of morphine on chlordiazepoxide-induced hyperdipsia in the water-deprived rat.

The effects of naloxone hydrochloride (0.01-10 mg X kg-1), naltrexone hydrochloride (0.01-10 mg X kg-1), and morphine sulphate (0.01-10 mg X kg-1) on the increased water consumption provoked by administration of chlordiazepoxide (10 mg X kg-1) were investigated in male rats which had been adapted to a 22 hr water-deprivation schedule. As previously reported, both naloxone and naltrexone dose-relatedly reduced water ingestion. Naloxone at 1 mg X kg-1 and naltrexone at 0.1 mg X kg-1 completely blocked the chlordiazepoxide-induced hyperdipsia. Since both opiate antagonists removed the chlordiazepoxide-induced effects in small doses, their effect can plausibly be attributed to opiate receptor blockade. Hence, chlordiazepoxide-induced hyperdipsia may depend upon the activation of endogenous opioid mechanisms. Morphine had little effect on drinking, unless a large dose (10 mg X kg-1) was used, when the thirst-induced and chlordiazepoxide-induced drinking were attenuated. The data provided no evidence that morphine, a mu opiate agonist, enhanced chlordiazepoxide-induced water consumption. The results are considered in relation to other relevant behavioural and biochemical findings.

Analysis of Variance↗

PubMed1984

Enhancement of saline consumption by chlordiazepoxide in thirsty rats: antagonism by Ro15-1788.

Water-deprived rats were given access to either water or a highly preferred 0.9% NaCl solution in a 30 min drinking test. The animals consumed substantially more saline than water. Chlordiazepoxide (2.5-20.0 mg/kg) was administered IP before the drinking test. Analysis of the results revealed a significant drug treatment X fluid condition interaction. Chlordiazepoxide produced a preferential enhancement of saline intake, achieving a peak effect at 5.0 mg/kg. Consideration of the time-course of drinking showed some complexity in the way in which chlordiazepoxide affected the saline drinking. During the first 6 min of the drinking period, the drug treatments tended to depress consumption, reaching a significant effect at 20.0 mg/kg. However, in the following 16 min interval of the drinking test, chlordiazepoxide significantly elevated saline consumption. The mechanism for this second effect may have been a retardation in the development of satiety. Finally, at the end of the drinking test, when saline consumption had become satiated, chlordiazepoxide exerted no discernible effect. The enhancement of saline consumption by chlordiazepoxide appears to have been benzodiazepine-receptor mediated, since the effect was reversed by treatment with Ro15-1788, a benzodiazepine receptor antagonist. The implications of a benzodiazepine-induced increase in salt intake are briefly considered. The over consumption of salt is contraindicated in certain clinical conditions. Both stress and hypertension are associated with elevated salt appetite. Treatment of these conditions using benzodiazepines may require due consideration of the possible stimulant effect of these drugs on salt appetite.

Animals↗

PubMed1992

Assessment of a cholinergic contribution to chlordiazepoxide-induced deficits of place learning in the Morris water maze.

This investigation sought to characterize the interaction between benzodiazepine and cholinergic systems in place learning in the Morris water maze. In the first experiment, rats were treated with scopolamine (1 mg/kg) alone or concomitantly with one of two doses of flumazenil (15 and 30 mg/kg) or with chlordiazepoxide (5 mg/kg) alone or concomitantly with flumazenil (15 mg/kg). Chlordiazepoxide and scopolamine severely impaired place learning but not cue learning. The low dose of flumazenil completely reversed the impairment produced by chlordiazepoxide and both high and low doses of flumazenil attenuated the place learning deficit produced by scopolamine. Neither dose of flumazenil affected place learning when administered alone. In the second experiment, rats were administered chlordiazepoxide (5 mg/kg) or scopolamine (1 mg/kg) alone or concomitantly with one of four doses of physostigmine (0.05, 0.10, 0.25, and 0.5 mg/kg). Once again, both chlordiazepoxide and scopolamine impaired place but not cue learning. Physostigmine reversed the impairment produced by scopolamine in a dose-dependent manner but failed at every dose to attenuate the impairment produced by chlordiazepoxide. The higher doses of physostigmine impaired place learning when administered alone. None of the drug treatments impaired cue learning. Together, these results suggest that the scopolamine-induced impairment of place learning is due to an increase in benzodiazepine/GABA activity, and contradict the notion that benzodiazepines impair memory by cholinergic mechanisms.

Acetylcholine↗

PubMed1994

Influence of microwave exposure on chlordiazepoxide effects in the mouse staircase test.

To ascertain whether behavioral effects of benzodiazepines are altered by exposure to microwave radiation, we compared the performance of male, Swiss CD1 mice in the staircase test 30 min after pretreatment with chlordiazepoxide (8, 16, and 32 mg/kg, IP) and immediately following a 5-min exposure to microwave radiation (4, 12, and 36 W/kg, continuous wave, 1.8 or 4.7 GHz). In this paradigm, chlordiazepoxide reduction in the number of rears (NR) and number of steps ascended (NSA) is postulated to reflect anxiolytic and sedative drug effects, respectively. In sham-exposed mice, increasing doses of chlordiazepoxide increased NSA without affecting NR, increased NSA and decreased NR, then decreased both NSA and NR. Microwave exposure generally did not alter NSA or NR in mice pretreated with lower doses of chlordiazepoxide. However, in mice pretreated with 32 mg/kg chlordiazepoxide, exposure to 36 W/kg microwave radiation significantly reversed the reductions in NSA and NR at 4.7 GHz but not at 1.8 GHz. These findings indicate that exposure to microwave radiation can selectively alter effects of chlordiazepoxide in this psychopharmacological paradigm.

Animals↗