Benzodiazepine mechanisms and drinking in the water-deprived rat.

Benzodiazepines (diazepam, midazolam, flurazepam and chlordiazepoxide) produced a hyperdipsia in rats which were well-adapted to a daily 22 hr water-deprivation schedule. The hyperdipsia occurred as a result of extensions in the time-course of drinking without impairment in the efficiency of drinking (rate of water intake). At doses larger than those associated with hyperdipsia, the rate of water consumption was markedly impaired, so that any extension in the duration of drinking was offset by the impaired efficiency. As a result, a non-monotonic relationship between dose of benzodiazepine and volume of water intake could be generated. The convulsant benzodiazepine, Ro5-3663, produced a reduction in drinking, at sub-convulsant doses and without general motor interference. This hypodipsia was completely reversed by concurrent treatment with either diazepam or midazolam. The results are discussed in terms of possible behavioural and biochemical mechanisms which may underlie benzodiazepine-induced hyperdipsia.