Hypothalamic paraventricular 5-hydroxytryptamine: receptor-specific inhibition of NPY-stimulated eating and energy metabolism.
The feeding effects of 5-hydroxytryptamine (5-HT)(1) and 5-HT(2) receptor agonists injected into the hypothalamic paraventricular nucleus (PVN) immediately prior to PVN administration of neuropeptide Y (NPY) were examined. The impact of these same compounds on NPY-induced alterations in energy metabolism was also assessed in an attempt to characterize further the potential interactive relationship of PVN NPY and 5-HT on feeding and whole body calorimetry. Specifically, several experiments examined the effect of various 5-HT receptor agonists on NPY-stimulated eating and alterations in energy substrate utilization [respiratory quotient (RQ)]. This included the 5-HT(1A) receptor agonist 8-OH-DPAT, the 5-HT(1B/1A) agonist RU 24969, the 5-HT(1D) agonist L-694,247, the 5-HT(2A/2C) agonist DOI, the 5-HT(2B) agonist BW 723C86 and the 5-HT(2C) agonist mCPP. In feeding tests conducted at the onset of the dark cycle, drugs were administered 5 min prior to PVN injection of NPY and food intake was measured 2 h postinjection. The metabolic effects of NPY following a similar pretreatment were monitored using an open-circuit calorimeter measuring the volume of oxygen consumed (VO(2)), carbon dioxide produced (VCO(2)) and RQ (VCO(2)/VO(2)). PVN injection of NPY (100 pmol) potentiated feeding and evoked reliable increases in RQ. Only DOI (2.5--5 nmol) pretreatment antagonized NPY-induced eating and blocked the peptide's effect on energy substrate utilization. Direct PVN pretreatment with spiperone (SPRN), a 5-HT(2A) receptor antagonist, and ketanserin (KTSN), a 5-HT(2A/2C) antagonist, but not SDZ SER 082, a 5-HT(2B/2C) antagonist, or the 5-HT(2C) antagonist RS 102221, blocked the effect of DOI in both feeding and metabolic tests providing additional evidence that activation of PVN 5-HT(2A) receptors inhibits NPY's action on feeding and substrate utilization.
Currie
Paul J
PJ
Department of Psychology, Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, USA. pjc37@columbia.edu
Coiro
Christina D
CD
Niyomchai
Tippy
T
Lira
Alena
A
Farahmand
Farnoosh
F
D000662:Amphetamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000662:Amphetamines; D009478:Neuropeptide Y; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine