Citalopram-induced hypophagia is enhanced by blockade of 5-HT(1A) receptors: role of 5-HT(2C) receptors.
The selective 5-hydroxytryptamine reuptake inhibitor citalopram (10 and 20 mg kg(-1), i.p.) significantly reduced food intake in male rats (CD-COBS) habituated to eat their daily food during a 4-h period. The 5-HT1A receptor antagonist WAY100635 (0.3 mg kg(-1)) administered systemically did not modify feeding but significantly potentiated the reduction in food intake caused by 10 mg kg(-1) i.p. citalopram. The dose of 5 mg kg(-1) i.p. citalopram was not active in animals pretreated with vehicle but significantly reduced feeding in animals pretreated with WAY100635. WAY100635 (0.1 microg 0.5 microl(-1)) injected into the dorsal raphe significantly potentiated the hypophagic effect of 10 mg kg(-1) citalopram. WAY100635 (1.0 microg 0.5 microl(-1)) injected into the median raphe did not modify feeding or the hypophagic effect of 10 mg kg(-1) citalopram. The 5-HT2B/2C receptor antagonist SB206553 (10 mg kg(-1), p.o.) slightly reduced feeding by itself but partially antagonized the effect of WAY100635 administered systemically (0.3 mg kg(-1), s.c.) or into the dorsal raphe (0.1 microg 0.5 microl(-1)) in combination with 10 mg kg(-1) i.p. citalopram. The hypophagic effect of 10 mg kg(-1) i.p. citalopram alone was not significantly modified by SB206553. Brain concentrations of citalopram and its metabolite desmethylcitalopram in rats pretreated with SB206553, WAY100635 and their combination were comparable to those of vehicle-pretreated rats, 90 min after citalopram injection. The hypophagic effect of citalopram was potentiated by blocking 5-HT1A receptors. Only the effect of the WAY100635/citalopram combination seemed to be partially mediated by central 5-HT2C receptors.
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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G
Grignaschi
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Invernizzi
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E
Fanelli
C
C
Fracasso
S
S
Caccia
R
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Samanin
D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007267:Injections; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D015283:Citalopram; D010879:Piperazines; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C015068:1-(3-chlorophenyl)piperazine