MINIMAL CHANGES WITH LONG-TERM ADMINISTRATION OF ANXIOLYTICS ON SEPTAL DRIVING OF HIPPOCAMPAL RHYTHMICAL SLOW ACTIVITY

In free-moving male rats, the function relating frequency to the thres hold current required to drive hippocampal rhythmical slow activity (R SA; ''theta'') with septal stimulation has a minimum at 7.7 Hz. Classi cal anxiolytics all increase thresholds in the region of 7.7 Hz, and s o does the novel anxiolytic buspirone. However, unlike classical anxio lytics, 2 or 3 weeks are normally required for the onset of the clinic al effects of buspirone. This study tested the effects of long-term ad ministration of chlordiazepoxide and buspirone on septal driving of RS A. Separate groups of naive rats received three IP injections per day of chlordiazepoxide (0.4 mg/kg), buspirone (0.1 mg/kg) or saline for 5 0 days. Both chlordiazepoxide and buspirone increased thresholds at 7. 7 Hz, as expected. These acute effects were not significantly changed with chronic administration. Buspirone and chlordiazepoxide produced s imilar, statistically significant, but small cumulative reductions in thresholds at 6.9 Hz. The present experiments suggest that if the effe cts of anxiolytic drugs on septally driven RSA provide any basis for t heir clinical action, then classical anxiolytics may have two actions: an immediate effect on euphoria and tension and a delayed effect on a nxiety proper - with buspirone sharing only the latter effect.