Effects of agents which interact with central benzodiazepine binding sites on stress-induced ultrasounds in rat pups.

Compounds of different chemical classes, with affinity for central benzodiazepine receptors, were investigated for effects on handling-induced ultrasonic cries in rat pups. Diazepam and clobazam inhibited ultrasounds and impaired motor performance at higher doses. Suriclone showed a similar profile to diazepam but premazepam clearly separated ultrasound inhibition from motor impairment. ZK 91296, CGS 9896, RU 39419 and RU 43028 inhibited ultrasounds with a lower maximal response but induced little or no motor incoordination. CL 218872 inconsistently inhibited sounds with no motor impairment and PK 8165 and PK 9084 had no consistent effects. Benzodiazepine antagonists weakly inhibited (RU 40410) or did not affect (Ro 15-1788 or CGS 8216) ultrasounds alone but fully (Ro 15-1788 or CGS 8216) or partially (RU 40410) antagonised the effects of benzodiazepines. Inverse agonists FG 7142, methyl-beta-carboline-3-carboxylate (BCM) and DMCM tended to increase ultrasounds alone, particularly when less stressful handling stimuli were used, and antagonised benzodiazepines. This procedure detects the differing behavioural effects of benzodiazepines receptor ligands and is proposed as a simple model of anxiety.