Extracellular hypothalamic serotonin levels after dorsal raphe nuclei stimulation of lean (Fa/Fa) and obese (fa/fa) Zucker rats.
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.
De Fanti
B A
BA
University of California, Division of Biological Sciences, Neurobiology, Physiology and Behavior, One Shields Avenue, Davis, CA 95616-8519, USA.
Gavel
D A
DA
Hamilton
J S
JS
Horwitz
B A
BA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017551:Microdialysis; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D012701:Serotonin