Intraventricular administration of cyclo(His-Pro), a metabolite of thyrotropin-releasing hormone (TRH), decreases water intake in the rat.

We explored the effect of cyclo(His-Pro) on drinking in water-deprived rats. Intraventricular administration of cyclo(His-Pro) significantly reduced water intake in these rats in a dose-dependent fashion (3 X 10(-10) -3 X 10(-8) mole), whereas its intraperitoneal injection did not cause any effect on water intake. The inhibitory potency of cyclo(His-Pro) was found to be similar to that of thyrotropin-releasing hormone (TRH), but cyclo(His-Pro) did not significantly interfere with TRH binding in the rat brain. The data indicate that cyclo(His-Pro) action was not mediated through the TRH counterpart. These results suggest that cyclo(His-Pro) may play a potential role in the regulation of water intake in the rat brain.