The present study examined the effects of dexamethasone and RU-38486 on the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electroencephalogram (EEG) of DBA/2J mice. Our data indicated that dexamethasone (1-10-100 micrograms/kg, ip) in a time- and dose-related manner significantly reduce the S&W occurrence in freely-moving DBA/2J mice. Cycloheximide (10 mg/kg, ip), a protein synthesis inhibitor, by itself did not modify significantly the S&W occurrence in mice, but when injected two hours before DEX (100 mg/kg, ip), induced consistent delay of DEX effects. On the other hand, treatment of mice with RU-38486 (50 mg/kg, ip) induced, after a transitory decrease, a dramatic increase of the rate of S&W episodes. In addition, we performed a "chemical adrenalectomy" treating mice with RU-38486 (50 mg/kg, po/d) for 4 days, and also in this case we observed a significant increase of S&W 24 h after the 4th treatment. Finally a series of experiments indicated that low doses of morphine inhibited, whereas high doses of naltrexone strongly enforced S&W. The present results suggest that glucocorticoids are able to modulate inherited spindling episodes in DBA/2J mice and that this effect may be related to a genomic activation mechanism. Studies in this field may give, in the near future, some important contributions to the understanding of corticosteroids involvement in brain excitability, and of their relationships with the opioid system.
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