Synergistic neurochemical and behavioral effects of fluoxetine and 5-HT1A receptor antagonists.
We studied the ability of WAY 100635 [N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide], 0.5 mg/kg, i.v. and (-)-5-Me-8-OH-DPAT [(-)-5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin], 3 mg/kg, i.v. two selective 5-HT1A receptor antagonists, to potentiate: (1) the enhancement of extracellular 5-HT levels ([5-HT(ext)]) induced by a single administration of 5 mg/kg i.p. fluoxetine using in vivo microdialysis in the ventral hippocampus of conscious rats, (2) the decrease in food intake induced by this antidepressant drug in food-deprived rats. The effects of fluoxetine were significantly potentiated, by 30-40%, by WAY 100635 as well as by (-)-5-Me-8-OH-DPAT in the two sets of experiments. Thus, fluoxetine increased [5-HT(ext)] in serotonergic nerve terminal areas and consequently, induced hypophagia, both effects being limited by indirect activation of somatodendritic 5-HT1A autoreceptors.
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Laboratoire de Neuropharmacologie UPRES JEMESR 92-372, Institut de Signalisation et Innovation Thérapeutique (IFR-ISIT), Université Paris Sud, Châtenay-Malabry, France. a-c.trillat@cep.u-psud.fr
Malagié
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Mathe-Allainmat
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Anmella
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Jacquot
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Langlois
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Gardier
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005473:Fluoxetine; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C113949:5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide