Acute effect of methyl bromide on sleep-wakefulness and its circadian rhythms in rats.

Key words : Methyl bromide—EEG—Wakefulness—Non-REM sleep—REM sleep— Bromine ions—Methanol Methyl bromide has been widely used as a fumigant in plant quarantine and agriculture, because of its strong insecticidal effect.1) However, methyl bromide is known to impair the function of the central nervous system (CNS) , when workers are exposed to it through inhalation and dermal contact. Disorders of the initiation and maintenance of sleep and wakefulness such as insomnia, somnolence, drowsiness and inebriation are observed in patients with methyl bromide intoxication, in addition to the main clinical symptoms such as vertigo, headache and unsteady gait.2-5) Recent studies with experimental animals have shown that methyl bromide induces changes in spontaneous locomotor activity,6,7) conditioned taste aversion,8) and brain levels of monoamines, acetylcholine and free amino acids9.10) as well as haematological and hepatological changes.11,12) In an attempt to clarify the acute effects of methyl bromide on the CNS, we investigated abnormal electrocorticographic activity and changes in sleep-wakeful-ness and its circadian rhythms after a single subcutaneous injection of methyl bromide in rats. The effects of possible hydrolysed products of methyl bromide, methanol and bromine ions on sleep and its rhythms were also examined. A total of 15 male rats of the Sprague Dawley strain were obtained at 4 weeks of age from Nihon CLEA, Ltd. Indwelling electrodes for EEG, EMG and EOG electrodes were implanted at 8 weeks of age. Two weeks were allowed for recovery from the implantation surgery and adaptation to the environment of polygraphic recordings. The methods of electrode implantation, polygraphic measurement and power spectral analysis of the cortical EEG activity were described previously.13) Wakefulness (W), non-REM sleep (NREMS) and REM sleep (REMS) were classified by visual inspection of the polygraphic records using the criteria described by Matsumoto et al.14) The rats were given food and water ad libitum. Illumination was controlled automatically by turning light on from 0800 h to 2000 h. Methyl bromide was dissolved in liquid paraffin to the concentration of 34 mg/ml. Because the LD50 of subcutaneously-administered methyl bromide was found to be 135 mg/kg body weight in a preliminary experiment, the methyl bromide solution was administered subcutaneously to 5 rats in each group at doses of 45 mg and 15 mg methyl bromide/kg body weight. The polygraphic recordings were made on Days 1, 3 and 5 and on Days 1 and 3 after 45 mg/kg and 15 mg/kg administration, respectively. Control values of W, NREMS and …