On the mechanism of serotonin-induced dipsogenesis in the rat.
Subcutaneous administration of l-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 micrograms/kg, IP), which also inhibits angiotensin II-induced drinking. Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 mg/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha 2-adrenergic agonist, clonidine (6.25 micrograms/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micrograms/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25 micrograms/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micrograms/kg, SC)-induced drinking was inhibited by cinanserin (25 micrograms/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that serotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.
D000818:Animals; D002216:Captopril / Q000008:administration & dosage; D002928:Cinanserin / Q000008:administration & dosage; D003000:Clonidine / Q000008:administration & dosage; D004327:Drinking Behavior / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage; D007545:Isoproterenol / Q000008:administration & dosage; D008784:Methysergide / Q000008:administration & dosage; D051381:Rats; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*
D012701:Serotonin; D002216:Captopril; D006220:Haloperidol; D002928:Cinanserin; D007545:Isoproterenol; D003000:Clonidine; D008784:Methysergide