RAT PUP ULTRASONIC VOCALIZATION - EFFECTS OF BENZODIAZEPINE RECEPTOR LIGANDS

The involvement of the GABA(A)-enzodiazepine receptor complex in rat p up ultrasonic vocalisations was studied by testing benzodiazepine rece ptor ligands with varying intrinsic activity and selectivity for benzo diazepine subtype receptors. Ultrasonic vocalisations were recorded un der two temperature conditions (37 degrees C and 18 degrees C), presum ably reflecting a low and high stress state. The latency to the negati ve geotaxis response, a measure of motor coordination and the rectal t emperature were determined to assess putative side effects of drugs. T he full, non-selective benzodiazepine receptor agonists diazepam, chlo rdiazepoxide, alprazolam and oxazepam suppressed ultrasonic vocalisati ons both at 37 degrees C and 18 degrees C conditions, although more ef ficaciously at 37 degrees C. The partial, non-selective benzodiazepine receptor agonist bretazenil and the partial benzodiazepine(1) selecti ve receptor agonist alpidem significantly reduced ultrasonic vocalisat ions at 37 degrees C, but not at 18 degrees C. The full benzodiazepine (1) selective receptor agonist zolpidem behaved like other fun, non-se lective benzodiazepine receptor agonists by reducing ultrasonic vocali sations under both high and low temperature. The effects of zolpidem i ndicate that activation of benzodiazepine(1) receptors alone already s uffices to suppress ultrasonic vocalisations. The non-selective, benzo diazepine receptor antagonist flumazenil and the partial, non-selectiv e benzodiazepine receptor inverse agonist FG 7142 (N'-methyl-beta-carb oline-3-carboxamide) and the full, non-selective benzodiazepine recept or inverse agonist DMCM ,7-dimethoxy-4-ethyl-beta-carboline-3-carboxyl ate) had no significant effect on ultrasonic vocalisations under both temperature conditions. The involvement of benzodiazepine receptors in rat pup ultrasonic vocalisations (37 degrees C-condition) was confirm ed by antagonism of the ultrasonic vocalisations reducing effects of c hlordiazepoxide by flumazenil (1 or 3 mg/kg). Using the rat pup ultras onic vocalisations paradigm under 18 degrees C and 37 degrees C condit ions combined with measurements of negative geotaxis-latencies and rec tal temperatures it is possible to (1) distinguish benzodiazepine rece ptor agonists from other anxiolytics because of dissimilar dose respon se curves at 37 degrees C and 18 degrees C, (2) differentiate partial from full receptor agonists by absence of effects at the 18 degrees C condition, (3) suggest a key role for benzodiazepine, receptors in the modulation of ultrasonic vocalisations. These data contribute to the predictive validity of pup vocalizations as an animal model of anxiety . (C) 1998 Elsevier Science B.V. All rights reserved.