Extracellular hypothalamic serotonin levels after dorsal raphe nuclei stimulation of lean (Fa/Fa) and obese (fa/fa) Zucker rats

Brain Res. 2000 Jun 30;869(1-2):6-14. doi: 10.1016/s0006-8993(00)02308-8.


Serotonin (5-HT), acting in the medial hypothalamus (MH), is involved in appetite/satiety and sympathetic stimulation of thermogenesis. This study tested the hypothesis that the enhanced energetic efficiency of obese Zucker rats is associated with a reduced capacity of activated dorsal raphe (DR) neurons to release 5-HT in the MH. We used microdialysis and HPLC-EC to measure dynamic changes in extracellular 5-HT levels in the MH of urethane-anesthetized, 10-14 week old male lean and obese Zucker rats. These concentrations did not differ significantly between the two genotypes prior to stimulation (mean+/-S.E.M.=3.8+/-0.5 fmol/microl, lean; 3.6+/-1.0 fmol/microl, obese) or following DR stimulation at 25 Hz (200 microA). The latter elicited initial net increases of 0.54+/-0.15 fmol/microl in lean and 0.58+/-0.20 fmol/microl in obese rats; and 20 min post-stimulus, 5-HT values were still elevated and comparable in the two genotypes. Although a 50-Hz (200 microA) stimulus evoked initial increases that were similar in lean (1.37+/-0.23 fmol/microl) and obese (0.95+/-0.24 fmol/microl,) rats, the net increase in 5-HT concentration during the next 20-40 min period was higher in the lean (2.03+/-0.55 fmol/microl vs. 1.18+/-0.24 fmol/microl in the obese animals). Also, in the lean, but not obese rats, extracellular 5-HT levels were significantly greater at 50 vs. 25 Hz. These results support the hypothesis that the capacity of midbrain serotonergic neurons to release 5-HT at the MH is reduced in obese Zucker rats, consistent with their blunted responsiveness to dietary stimuli and greater energetic efficiency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Electric Stimulation
  • Male
  • Mesencephalon / metabolism
  • Mesencephalon / pathology
  • Mesencephalon / physiopathology
  • Microdialysis
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Obesity / physiopathology*
  • Raphe Nuclei / metabolism*
  • Raphe Nuclei / pathology
  • Raphe Nuclei / physiopathology
  • Rats
  • Rats, Zucker
  • Serotonin / metabolism*
  • Signal Transduction / physiology
  • Ventromedial Hypothalamic Nucleus / metabolism*
  • Ventromedial Hypothalamic Nucleus / pathology
  • Ventromedial Hypothalamic Nucleus / physiopathology


  • Serotonin