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

Brant A. De Fanti, David A. Gavel, Jock S. Hamilton, Barbara A Horwitz

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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/μl, lean; 3.6±1.0 fmol/μl, obese) or following DR stimulation at 25 Hz (200 μA). The latter elicited initial net increases of 0.54±0.15 fmol/μl in lean and 0.58±0.20 fmol/μl 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 μA) stimulus evoked initial increases that were similar in lean (1.37±0.23 fmol/μl) and obese (0.95±0.24 fmol/μl,) 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/μl vs. 1.18±0.24 fmol/μl 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. Theme: Neurotransmitters, modulators, transporters, and receptors. Topic: Serotonin. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)6-14
Number of pages9
JournalBrain Research
Volume869
Issue number1-2
DOIs
StatePublished - Jun 30 2000

Fingerprint

Zucker Rats
Serotonin
Middle Hypothalamus
Neurotransmitter Transport Proteins
Genotype
Serotonergic Neurons
Dorsal Raphe Nucleus
Neurotransmitter Receptor
Thermogenesis
Urethane
Microdialysis
Appetite
Mesencephalon
High Pressure Liquid Chromatography
Neurons

Keywords

  • Electrical stimulation
  • Microdialysis
  • Ventromedial hypothalamus
  • VMH

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Extracellular hypothalamic serotonin levels after dorsal raphe nuclei stimulation of lean (Fa/Fa) and obese (fa/fa) Zucker rats. / De Fanti, Brant A.; Gavel, David A.; Hamilton, Jock S.; Horwitz, Barbara A.

In: Brain Research, Vol. 869, No. 1-2, 30.06.2000, p. 6-14.

Research output: Contribution to journalArticle

De Fanti, Brant A. ; Gavel, David A. ; Hamilton, Jock S. ; Horwitz, Barbara A. / Extracellular hypothalamic serotonin levels after dorsal raphe nuclei stimulation of lean (Fa/Fa) and obese (fa/fa) Zucker rats. In: Brain Research. 2000 ; Vol. 869, No. 1-2. pp. 6-14.
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abstract = "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/μl, lean; 3.6±1.0 fmol/μl, obese) or following DR stimulation at 25 Hz (200 μA). The latter elicited initial net increases of 0.54±0.15 fmol/μl in lean and 0.58±0.20 fmol/μl 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 μA) stimulus evoked initial increases that were similar in lean (1.37±0.23 fmol/μl) and obese (0.95±0.24 fmol/μl,) 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/μl vs. 1.18±0.24 fmol/μl 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. Theme: Neurotransmitters, modulators, transporters, and receptors. Topic: Serotonin. Copyright (C) 2000 Elsevier Science B.V.",
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