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d-Fenfluramine- and d-norfenfluramine-induced hypophagia: differential mechanisms and involvement of postsynaptic 5-HT receptors.

Abstract：

:Severe depletion of 5-hydroxytryptamine (5-HT) by para-chlorophenylalanine (pCPA, 150 mg/kg per day x3) did not alter the hypophagic effect of d-fenfluramine (1-3 mg/kg i.p.) 1 h after food presentation in 24-h food-deprived rats, and moderately and comparably increased the hypophagic effects of its metabolite, d-norfenfluramine (0.35-1.0 mg/kg i.p.), and of the 5-HT1C receptor agonist, 1-(3-chlorophenyl)piperazine (mCPP; 1.5, 2.0 mg/kg i.p.). Chronic treatment with mCPP (2.5 mg/kg i.p. x 14) attenuated the hypophagia induced by d-norfenfluramine (1, 1.5 mg/kg) but not d-fenfluramine (1, 3 mg/kg). 1-(1-Naphthyl)piperazine (3, 8 mumol/kg s.c.), which has greater affinity for 5-HT1C than for 5-HT2 receptors, had no effect on the hypophagia induced by d-fenfluramine (1.25, 2.0 mg/kg), but 1.3 and 3 mumol/kg 1-(1-naphthyl)piperazine largely and comparably attenuated the substantial hypophagic effect of d-norfenfluramine (0.75 mg/kg). The essentially complete hypophagic action of d-norfenfluramine (1.25 mg/kg) was inhibited by 1-(1-naphthyl)piperazine with ID50 = 2.13 mumol/kg. Ketanserin, which binds more weakly than 1-(1-naphthyl)piperazine to 5-HT1C receptors and more strongly to 5-HT2 receptors, attenuated weaker but not stronger hypophagic effects of d-fenfluramine (1.25, 2.0 mg/kg) when given at high dosage (8, 16 mumol/kg s.c.). Ketanserin (16 mumol/kg) also weakly attenuated the hypophagia due to d-norfenfluramine (0.75 mg/kg), but not the essentially complete hypophagia due to d-norfenfluramine (1.25 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Gibson EL,Kennedy AJ,Curzon G

doi

10.1016/0014-2999(93)90013-8

subject

Has Abstract

pub_date

1993-09-21 00:00:00

pages

83-90

issue

1

eissn

0014-2999

issn

1879-0712

pii

0014-2999(93)90013-8

journal_volume

242

pub_type

杂志文章

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