Hypothalamic paraventricular 5-hydroxytryptamine: receptor-specific inhibition of NPY-stimulated eating and energy metabolism

Pharmacol Biochem Behav. 2002 Apr;71(4):709-16. doi: 10.1016/s0091-3057(01)00671-2.


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.

MeSH terms

  • Amphetamines / antagonists & inhibitors
  • Amphetamines / pharmacology
  • Animals
  • Eating / drug effects*
  • Energy Metabolism / drug effects*
  • Male
  • Neuropeptide Y / antagonists & inhibitors
  • Neuropeptide Y / pharmacology*
  • Oxygen Consumption / drug effects
  • Paraventricular Hypothalamic Nucleus / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT1
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Stimulation, Chemical


  • Amphetamines
  • Neuropeptide Y
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • 4-iodo-2,5-dimethoxyphenylisopropylamine