In vivo increase in hypothalamic cyclic AMP following 5-hydroxytryptophan administration in rats.
The administration of 5-hydroxytryptophan (5-HTP, 100 mg/kg, i.p.) consistently increased hypothalamic cyclic AMP levels in rats treated 10 days earlier with the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), to produce 5-HT receptor supersensitivity. However 5-HTP (100 mg/kg), failed to cause an increase in hypothalamic cyclic AMP in rats not pretreated with 5,7-DHT. The 5-HTP-induced increase in cyclic AMP was blocked by the decarboxylase inhibitor, benserazide (RO 4-4602, 800 mg/kg) and by the 5-HT antagonist metergoline (5 mg/kg). Other treatments that caused a significant elevation of hypothalamic cyclic AMP included: (a) L-Tryptophan plus the monoamine oxidase inhibitor, tranylcypromine, and (b) the serotonin agonist, 1-(m-trifluromethylphenyl)-1-piperazine. The 5-HT antagonist, methysergide, blocked the serotonin receptor mediated behavioral syndrome, but failed to prevent the increase in hypothalamic cyclic AMP. Moreover, the 5-HT agonist, 5-methoxy-N, N-dimethyltryptamine, (5-Me-DMT), induced a strong behavioral syndrome but failed to significantly increase hypothalamic cyclic AMP. These findings suggest that activation of 5-HT receptors somewhere in the brain causes an increase in hypothalamic cyclic AMP, but further studies will be needed to determine whether this is a direct result of activation of the 5-HT receptors in the hypothalamus.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D010879:Piperazines; D012702:Serotonin Antagonists; D008711:Metergoline; C018406:1-(3-trifluoromethylphenyl)piperazine; D015116:5,7-Dihydroxytryptamine; D014191:Tranylcypromine; D001545:Benserazide; D014364:Tryptophan; D011433:Propranolol; D006916:5-Hydroxytryptophan; D000242:Cyclic AMP; D008784:Methysergide