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/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.