Effects of d-fenfluramine on feeding and hypothalamic 5-hydroxytryptamine and dopamine in male and female rats.
Male and female rats were given d-fenfluramine and its effects on feeding and on hypothalamic concentrations of the drug, its metabolite norfenfluramine and 5-hydroxytryptamine (5-HT) and dopamine determined. ID50 values (i.p.) for the hypophagic effect of the drug on 30-, 42- and 100-day-old rats measured over 2 h during the light phase after 24 h food deprivation did not vary significantly with sex but tended to decrease with age approximately in parallel with daily percentage increases and (after deprivation) of decreases in body weight. However, male but not female 30-day-old rats showed a rebound of feeding during the subsequent 2 h. ID50 values of 42-day-old rats on a palatable diet or measured during the dark phase when freely feeding also did not vary with sex. Male 30-day-old rats killed at 2-10 h after an ID75 (p.o.) dose of d-fenfluramine had substantially lower hypothalamic concentrations of the drug and comparable or slightly lower concentrations of its metabolite norfenfluramine than 30-day-old females. Similarly treated 100-day-old males also had lower concentrations of fenfluramine but significantly higher norfenfluramine levels than females so that drug plus metabolite concentrations were essentially independent of sex. 100-day-old females killed 2 h, 24 h and 7 days after d-fenfluramine (3.8 mg/kg p.o. = ID75) had larger percentage decreases of hypothalamic 5-HT than identically treated males. Percentage decreases of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) tended to become less marked with time after injection in males but not females.(ABSTRACT TRUNCATED AT 250 WORDS)
Oluyomi
A O
AO
Department of Neurochemistry, Institute of Neurology, Queen Square, London, UK.
Datla
K P
KP
Curzon
G
G
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005277:Fenfluramine / Q000493:pharmacokinetics / Q000494:pharmacology*; D005508:Food Deprivation; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012727:Sex Characteristics
D015102:3,4-Dihydroxyphenylacetic Acid; D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine