Effects of dexfenfluramine and opioid peptides, alone or in combination, on food intake and brain serotonin turnover in rats.
Dexfenfluramine (d-FF) and opiate agonists both act on food intake but in opposite ways. Serotonin is known to be involved in the pharmacological action of both d-FF and opiates, but not necessarily in the feeding effect of the latter. In order to test this hypothesis, the effects of three opioid agonists, beta-endorphin, dynorphin and D-Ser2-Leu-Enk-Thr6 (DSLET) and of an antagonist, naltrexone, were investigated individually and in combination with d-FF on food intake and brain serotonin turnover. The opioid agonist-d-FF combinations generally produced a similar anorectic effect to that of d-FF alone, with the exception of DSLET which showed a reciprocal antagonism. The serotonergic effects varied according to the opioid tested, alone or in combination with d-FF. This does not allow to highlight a general pattern of serotonin involvement in the feeding effects of these peptides. However, all the treatments which decreased feeding (d-FF, naltrexone and the combinations dynorphin-d-FF and beta-endorphin-d-FF) displayed similar trends in hypothalamic serotonergic variations. This study evidences a role of serotonin in the feeding effect of opiates, although not similar for all of them. The use of d-FF provides a tool for assessing this involvement.
Laboratoire de Pharmacologie, U.R.A.-CNRS 594, Faculté de Pharmacie, Châtenay-Malabry, France.
J J
JJ
Robert
M
M
Orosco
C
C
Rouch
Y
Y
Cohen
C
C
Jacquot
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D001615:beta-Endorphin / Q000494:pharmacology
D004723:Endorphins; D005277:Fenfluramine; D012701:Serotonin; D004743:Enkephalin, Leucine; D009271:Naltrexone; D001615:beta-Endorphin; D004399:Dynorphins; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-