Received for publication March 28, 2005.
Revised August 2, 2005.
Accepted for publication August 2, 2005.

Despite Similar Anxiolytic Potential, the 5-HT_2C Receptor Antagonist SB-242084 and Chlordiazepoxide Produced Differential Effects on EEG Power Spectra

Abstract

Serious efforts have been made to develop anxiolytics with improved clinical utility and reduced side effects. 5-HT_2C receptor antagonists are potential anxiolytics, however, their effects on vigilance are not well characterized. To compare the effects of benzodiazepines and subtype-selective 5-HT_2C receptor antagonists on anxiety, vigilance and EEG power density, social interaction test and polygraphic recordings were performed in male Sprague-Dawley rats after chlordiazepoxide (CDP, 4.0 mg/kg i.p) and SB-242084 (0.1, 0.3 and 1.0 mg/kg, i.p.) treatment. CDP and SB-242084 (0.3 and 1.0 mg/kg) had similar anxiolytic effects. Spectral analysis of EEG in wakefulness (W) and paradoxical sleep showed an opposite effect on theta activity (5-9 Hz); decreased after CDP, while increased after SB-242084. In addition, CDP significantly decreased slow wave activity (0.5-4 Hz) in deep slow wave sleep (SWS-2) and increased power at frequencies above 12 Hz mainly in W and paradoxical sleep (PS). A markedly increased intermediate stage of sleep was also found in the second h after CDP treatment. At the highest dose SB-242084 increased W along with theta activity and decreased SWS-2. In summary, low but potent anxiolytic doses of the subtype-selective 5-HT_2C receptor antagonist SB-242084 did not affect vigilance states but caused an increased theta activity in W, raising the possibility of a cognitive-enhancing effect of the drug. In contrast, acute CDP administration, based on spectral analysis of the EEG, produced a more superficial sleep along with a decreased theta activity.

Key words: 5-HT2C receptor, EEG power spectra, SB-242084, benzodiazepine, sleep, theta activity