Caffeine-induced hypodipsia in water-deprived rats: relationships with benzodiazepine mechanisms

The effects of caffeine (3-100 mg/kg) on water intake and the time course of drinking were investigated in male rats which had been adapted to a daily 22 hr water deprivation schedule. Doses of caffeine were found which significantly depressed water intake, reduced the time to the first interruption in drinking, and depressed the time course of drinking, without manifestly affecting the efficiency of drinking. At the highest dose, however, caffeine had a major suppressant effect on drinking, which was accompanied by signs of motor interference. The hypodipsic effect of caffeine was reversed by benzodiazepine treatment (midazolam or diazepam). However, the convulsant benzodiazepine Ro5-3663 which on electrophysiological evidence can act as a GABA antagonist also reduced drinking, adding to the hypodipsic effect of caffeine. A water load prior to the drinking test produced satiation effects, closely reminiscent of the effects of caffeine at lower doses. The possible mimicry of thirst satiety by caffeine is discussed, together with possible underlying mechanisms of caffeine-benzodiazepine interactions.