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 language | English (US) |
|---|---|
| Pages (from-to) | 6-14 |
| Number of pages | 9 |
| Journal | Brain Research |
| Volume | 869 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jun 30 2000 |
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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 journal › Article
}
TY - JOUR
T1 - Extracellular hypothalamic serotonin levels after dorsal raphe nuclei stimulation of lean (Fa/Fa) and obese (fa/fa) Zucker rats
AU - De Fanti, Brant A.
AU - Gavel, David A.
AU - Hamilton, Jock S.
AU - Horwitz, Barbara A
PY - 2000/6/30
Y1 - 2000/6/30
N2 - 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.
AB - 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.
KW - Electrical stimulation
KW - Microdialysis
KW - Ventromedial hypothalamus
KW - VMH
UR - http://www.scopus.com/inward/record.url?scp=0034733883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034733883&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(00)02308-8
DO - 10.1016/S0006-8993(00)02308-8
M3 - Article
C2 - 10865053
AN - SCOPUS:0034733883
VL - 869
SP - 6
EP - 14
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -