Peripheral conversion of L-5-hydroxytryptophan to serotonin induces drinking in rats.
Female rats administered serotonin (0.25 to 4.0 mg/kg, s.c.) showed a dose-dependent increase in water intake. The dipsogenic response was nearly maximal when 2 mg/lg was administered s.c. and plateaued by 2 hr after treatment. l-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, is also a potent dipsogen which induces drinking by way of the renin-angiotensin system. The possibility that the dipsogenic activity of 5-HTP is dependent on decarboxylation to serotonin was the objective of these studies. Either benserazide (30 mg/kg. s.c.), a central and peripheral decarboxylase inhibitor, or carbidopa (6.5 mg/kg, s.c.), a peripheral decarboxylase inhibitor, was administered 15 min prior to the dipsogen. Both decarboxylase inhibitors attenuated the dipsogenic response to 5-HTP (25 mg/kg, s.c.) but not to serotonin (2 mg/kg, s.c.). The peripheral serotonergic receptor antagonist, methysergide (3 mg/kg, i.p.), blocked the dipsogenic responses to both 5-HTP (25 mg/kg, s.c.) and serotonin (2 mg/kg, s.c.). There was no interaction between 5-HTP (18 mg/kg, s.c.) and serotonin (1 mg/kg, s.c.) when administered simultaneously with respect to their dipsogenic effects. Thus, the drinking response accompanying administration of 5-HTP occurs following peripheral conversion to serotonin which, in turn, activates peripheral serotonergic receptors. The mechanisms(s) by which activation of peripheral serotonergic receptors increases water intake is not known, but appears to involve release of renin from the kidney.
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000502:physiology*; D005260:Female; D008784:Methysergide / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000096:biosynthesis* / Q000502:physiology
D011985:Receptors, Serotonin; D012701:Serotonin; D001545:Benserazide; D006916:5-Hydroxytryptophan; D002230:Carbidopa; D008784:Methysergide