ONTOGENIC CHANGES IN RESPONSIVENESS TO BENZODIAZEPINE RECEPTOR LIGANDS ON ULTRASONIC VOCALIZATIONS IN RAT PUPS

The ontogenetic changes in responsiveness to benzodiazepine receptor l igands on ultrasonic vocalizations in rat pups from the age of day 3 t o day 12 were evaluated. Rat pups, while separated from their dam and littermates and placed in a cold environment, emit ultrasonic vocaliza tions. These ultrasonic calls became attenuated dose-dependently in nu mber and power after administration of the anxiolytic diazepam (0.25-1 .0 mg/kg, sc), but the inhibitory effect of diazepam at the highest do se was less on day 6 and day 9. Moreover, type I benzodiazepine recept or ligands, Ro16-6028 and Ro23-0364 (0.5-2.0 mg/kg, sc), also dose-dep endently attenuated the ultrasonic vocalizations 30-60 min after injec tion. The inhibitory effects of these drugs became more pronounced wit h the increasing age of the pup, and they were equivalent on day 12 to those in adult rats. These results suggest that different ontogenetic changes in development of two subtypes of central benzodiazepine rece ptors of pups might be related in the psychopharmacological mediation of the ultrasonic vocalization.