title: Effects of tryptophan and of 5-hydroxytryptamine receptor subtype agonists on feeding.
abstract: Feeding or food withdrawal can affect the supply of tryptophan to the brain and hence (in some circumstances) 5-HT synthesis therein. Also fenfluramine which releases 5-HT to postsynaptic receptors suppresses appetite and there are reports that tryptophan can have a similar effect. Furthermore, feeding is reported to release hypothalamic 5-HT. Therefore 5-HT could have a role in the normal termination of feeding and perhaps also in disorders of appetite. The recognition of various 5-HT receptor subtypes has stimulated research in this area. We have now investigated the involvement of the subtypes in the pharmacological control of feeding. Thus, 5-HT1A agonists (8-OH-DPAT, buspirone, gepirone etc.) stimulate intake in freely feeding rats, probably by activating autoreceptors on the cell bodies of 5-HT neurons so that 5-HT release at terminals is decreased. The hyperphagia is not explicable by increased activity or gnawing and is strikingly manifest against carbohydrate in carbohydrate vs. protein choice experiments. Feeding in previously food deprived rats is decreased by the 5-HT agonists RU 24969, 1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl) phenyl]piperazine (TFMPP). Effects of antagonists suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors only while mCPP and TFMPP induce hypophagia at 5-HT1C sites, though this effect also requires 5-HT1B receptors for its expression. Responsible sites occur in the paraventricular nucleus of the hypothalamus as infusing either RU 24969 or TFMPP therein causes hypophagia. On systemic injection, the hypophagic drugs are particularly active in female rats, an effect of conceivable relevance to human anorexic illness.
authors.affiliation: Institute of Neurology, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Curzon
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005508:Food Deprivation; D005518:Food Preferences / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012737:Sex Factors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology*
chemical_list: D004040:Dietary Carbohydrates; D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014364:Tryptophan; C015068:1-(3-chlorophenyl)piperazine