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Recent studies using melanocortin-4 receptor (MC4R) knockout mice and MC4R antagonists have shown that weakening of MC4R-ergic tone increases food intake and causes obesity. In this study, we used the newly discovered selective MC4R antagonist HS014 for increasing food intake in free-feeding rats and evaluated the effects of the NPY Y1 receptor antagonist 1229U91 and the selective serotonin uptake inhibitor fluoxetine on this increased feeding behavior. 1229U91 (12 nmol, i.c.v.), which alone does not affect food intake, significantly attenuated the orexigenic effects of HS014, whereas 1 and 3 nmol doses of 1229U91 were ineffective. Fluoxetine, which has been shown to inhibit NPY release, inhibited spontaneous food intake and completely blocked the stimulation of food intake by HS014. These data suggest that feeding induced by weakening of the MC4R-ergic tone may be mediated through activation of the NPY-ergic system. This is the first report showing that physiological feeding response evoked by MC4R blockage is influenced by NPY signalling. Copyright 1998 Academic Press.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9675121&dopt=Abstract
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Pharmacol Biochem Behav. 1998 Jul;60(3):719-25.
Selective serotonin reuptake inhibitors may enhance responses to noxious stimulation.
Dirksen R, Van Luijtelaar EL, Van Rijn CM.
NICI/Experimental Anesthesiology, University of Nijmegen, The Netherlands.
The acute effects of various doses of two selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine) on thermal and electrical stimulation-induced pain were investigated in drug-naive Wistar rats. The hot-plate and the tail-flick test and the noxious-induced withdrawal test were used. The two drugs had no effects on heat-induced pain behavior. However, the two compounds enhanced the motor responses induced by noxious electrical stimulation. These data contrast to what is generally found for tricyclic antidepressants and suggest a modality specific pain system. Cardiac and blood pressure were also found to change, but these changes were not correlated to changes in nociception. Taken together, the data suggest that the acutely administered selective serotonin reuptake inhibitors may exacerbate an acute type of pain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9678656&dopt=Abstract
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Neuropharmacology. 1998;37(2):243-50.
The role of central 5-HT receptors in the bronchoconstriction evoked by inhaled capsaicin in anaesthetised guinea-pigs.
Bootle DJ, Adcock JJ, Ramage AG.
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, UK.
The effects of intracisternal (i.c) injections of the 5-HT1A receptor agonists, buspirone and 8-OH-DPAT, and the antagonists WAY-100635; and (-)-pindolol, the 5-HT1B/1D receptor agonist sumatriptan and antagonist GR127935, the 5-HT2 receptor agonist DOI and the antagonist cinanserin, the 5-HT3 receptor antagonist granisetron, the alpha-adrenoceptor agonist clonidine and the antagonist idazoxan, the D2 receptor antagonists (-)-sulpiride and the 5-HT uptake inhibitor fluoxetine on capsaicin-evoked increase in tracheal inflation pressure (bronchoconstriction) were investigated in alpha-chloralose anaesthetised, neuromuscularly blocked, artificially ventilated guinea-pigs. Buspirone, 8-OH-DPAT and fluoxetine significantly potentiated while WAY-100635 (-)-pindolol and sumatriptan attenuated the evoked bronchoconstriction when applied i.c. Granisetron attenuated the response when applied i.v. but not when given i.c. The 5-HT2, alpha2-adrenoceptor and D2 dopamine receptor ligands did not have any significant effect on the evoked bronchoconstriction. Pretreatment i.v. with WAY-100635 alone had no effect on the capsaicin-evoked bronchoconstriction but blocked the potentiating action of i.c. buspirone. The effects of sumatriptan could be completely blocked by pretreatment i.v. with GR127935. Only DOI, in the presence (i.v.) of the peripheral acting 5-HT2 receptor antagonist BW501C67, caused a significant increase in baseline tracheal inflation pressure. It is concluded that activation of central 5-HT1A and 5-HT1B/1D receptors have opposing roles, facilitation and inhibition respectively, on the reflex activation of bronchoconstrictor vagal preganglionic neurones.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9680249&dopt=Abstract
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