SIMILAR EFFECTS OF BUSPIRONE AND CHLORDIAZEPOXIDE ON A FIXED-INTERVALSCHEDULE WITH LONG-TERM, LOW-DOSE ADMINISTRATION

Buspirone is a novel anxiolytic which does not share the muscle relaxa nt, anticonvulsant and sedative properties of classical anxiolytics su ch as the benzodiazepines. Its effects on behavioural tests of anxioly tic action generally match those of classical anxiolytics provided a l ow dose is used. However, in a previous experiment, buspirone appeared to affect fixed interval responding in a way which differed qualitati vely as well as quantitatively from the classical anxiolytic chlordiaz epoxide. It takes as much as 2 weeks for the clinical effects of anxio lytics to develop, during which time the side effects of benzodiazepin es undergo tolerance. We, therefore, decided to compare long-term pre- administration (60 days, three injections/day) of buspirone and chlord iazepoxide on learning of a fixed interval 60-s schedule. The doses we re based on previous acute dose-response tests of hippocampal theta rh ythm in freely moving animals. Buspirone (0.1 mg/kg i.p.) and chlordia zepoxide (0.4 mg/kg i.p.) produced similar increases in responding, es pecially in the middle of acquisition of the fixed interval schedule. Consistent with our acute electrophysiological tests, the effects of 0 .4 mg/kg chlordiazepoxide were somewhat larger than those of 0.1 mg/kg buspirone. These results suggest that the acute effects of buspirone, but probably not chlordiazepoxide, on fixed interval responding are c ontaminated by side effects which do not seriously affect the results with long-term administration. The effects of both novel and classical anxiolytics on control of hippocampal theta rhythm appear to predict the magnitude of their common anxiolytic effects and to be unrelated t o their different side effects.