Effect of the intracerebroventricular administration of GR 113808, a selective 5-HT4 antagonist, on water intake during hyperosmolarity and hypovolemia

We demonstrate here that acute third ventricle injections of GR 113808, a h ighly selective 5-HT4 antagonist, decrease water intake induced by a previo us salt load while potentiating drinking elicited by hypovolemia induced by previous subcutaneous administration of polyethylene glycol in male Wistar rats (200 +/- 20 g). At the dose of 160 nmol/rat, third ventricle injectio ns of GR 113808 induced a significant reduction of water intake in salt-loa ded animals after 120 min as compared to salt-loaded animals receiving thir d ventricle injections of saline (salt load + GR = 3.44 +/- 0.41 ml, N = 12 ; salt load + saline = 5.74 +/- 0.40 mi, N = 9). At the dose of 80 nmol/rat , GR 113808 significantly enhanced water intake in hypovolemic animals afte r 120 min as compared to hypovolemic animals receiving third ventricle inje ctions of saline (hypovol + GR = 4.01 +/- 0.27 ml, N = 8; hypovol + saline = 2.41 +/- 0.23 ml, N = 12). We suggest that central 5-HT4 receptors may ex ert a positive drive on water intake due to hyperosmolarity and a negative input on drinking provoked by hypovolemia.