Benzodiazepines and putative 5-HT1A agonists increase hypertonic saline consumption in rehydrating rats

Male rats were adapted to a 22 hr water-deprivation schedule, and to a 30 min test of hypertonic (1.8 or 2.7%) NaCl solution ingestion. A novel benzodiazepine, Ro23-0364, recently reported to have anxiolytic activity in rats and squirrel monkeys but to have limited potential to produce unwanted side effects, produced significant dose-related increases in hypertonic saline ingestion. Midazolam, a benzodiazepine full agonist, increased salt intake but the effect was offset at higher doses by the induction of sedation. Three putative 5-HT1A agonists, proposed as nonbenzodiazepine-related anxiolytics, were also tested: the highly selective 8-OH-DPAT, gepirone and ipsapirone (TVX Q 7821). In each case, occasions when hypertonic saline consumption was significantly increased were detected. At 300 micrograms/kg of 8-OH-DPAT and 10 mg/kg of gepirone, the appearance of a pronounced flattened body posture effectively interfered with drinking responses. It appears possible that a behavioural action shared by benzodiazepines and 5-HT1A agonists may be responsible for the increased hypertonic saline ingestion.