Differential effects of the 5-HT 1B/2C receptor agonist mCPP and the 5-HT1A agonist flesinoxan on hypothalamic neuropeptide Y in the rat: evidence that NPY may mediate serotonin's effects on food intake.
To determine whether NPY and 5-HT interact, we studied the effects on hypothalamic NPY and NPY mRNA levels of acute (10 mg/kg) and 7-day administration (10 mg/kg/day) of mCPP (a 5-HT 1B/2C agonist) and flesinoxan (a 5-HT 1A agonist). After both treatments, mCPP reduced food intake and NPY levels in the PVN (p < 0.01). NPY mRNA levels were only increased by comparable food restriction (p < 0.05). Acute flesinoxan injection increased food intake and NPY levels in the PVN and ARC (p < 0.01). This suggests that food intake changes induced by mCPP and flesinoxan are associated with altered NPYergic activity. Stimulation of different hypothalamic 5-HT1 receptors may alter NPY levels available for release in the PVN, possibly by altering transport along the ARC-PVN projection. Therefore, inhibition of the ARC-PVN projection may at least partly mediate the hypophagic effects of serotonin.
Department of Medicine, University of Liverpool, UK.
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Dryden
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Frankish
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Williams
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D006728:Hormones; D009478:Neuropeptide Y; D010879:Piperazines; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C056895:flesinoxan; C015068:1-(3-chlorophenyl)piperazine