Enhancement of saline consumption by chlordiazepoxide in thirsty rats: antagonism by Ro15-1788.

Water-deprived rats were given access to either water or a highly preferred 0.9% NaCl solution in a 30 min drinking test. The animals consumed substantially more saline than water. Chlordiazepoxide (2.5-20.0 mg/kg) was administered IP before the drinking test. Analysis of the results revealed a significant drug treatment X fluid condition interaction. Chlordiazepoxide produced a preferential enhancement of saline intake, achieving a peak effect at 5.0 mg/kg. Consideration of the time-course of drinking showed some complexity in the way in which chlordiazepoxide affected the saline drinking. During the first 6 min of the drinking period, the drug treatments tended to depress consumption, reaching a significant effect at 20.0 mg/kg. However, in the following 16 min interval of the drinking test, chlordiazepoxide significantly elevated saline consumption. The mechanism for this second effect may have been a retardation in the development of satiety. Finally, at the end of the drinking test, when saline consumption had become satiated, chlordiazepoxide exerted no discernible effect. The enhancement of saline consumption by chlordiazepoxide appears to have been benzodiazepine-receptor mediated, since the effect was reversed by treatment with Ro15-1788, a benzodiazepine receptor antagonist. The implications of a benzodiazepine-induced increase in salt intake are briefly considered. The over consumption of salt is contraindicated in certain clinical conditions. Both stress and hypertension are associated with elevated salt appetite. Treatment of these conditions using benzodiazepines may require due consideration of the possible stimulant effect of these drugs on salt appetite.