Meal-induced changes in extracellular 5-HT in medial hypothalamus of lean (Fa/Fa) and obese (fa/fa) Zucker rats

Hypothalamic serotonin (5-MT) is involved in appetite regulation and sympat hetic stimulation of thermogenesis. This study tested the hypothesis that t he enhanced energetic efficiency of obese Zucker rats involves blunted sero tonergic release within the medial hypothalamus (MH). We used microdialysis and HPLC-EC to measure dynamic changes in extracellular 5-HT levels in the MH of 10-13-week-old male lean (Fa/Fa) and obese (fa/fa) Zucker rats befor e and after a meal. No differences were noted in basal levels of 5-HT betwe en lean and obese rats. Consistent with the suggestion that hypothalamic 5- HT plays a physiological role in feeding, extracellular 5-HT levels increas ed significantly in both lean and obese rats given a meal. This increase wa s observed in the 20 min interval in which they ate the 8.1 kcal meal and r emained for an additional 60 min. The net release of 5-HT during the meal i nterval was comparable in the lean (1.46 +/-0.38 moll/mul) and obese (1.21 +/-0.82 fmol/mul) rats. However, the 5-HT levels of the leans (1.80 +/-0.29 fmol/mul) plateaued in the next 20 min interval, whereas they continued ri sing (2.74 +/-0.53 fmol/mul) in obese rats and were significantly higher th an those in the leans during the 40 and 60 min intervals after the meal was presented. This resulted in a total net release during the meal plus the n ext three 20 min intervals that was significantly higher in obese (9.83 +/- 1.16 fmol/mu1) than in lean (5.59 +/-0.85 fmol/mul) rats. Thus, the enhance d energetic efficiency of the obese Zucker rats may not be associated with attenuated serotonin release in response to a meal. Rather their enhanced r elease of 5-HT in the MH may reflect compensatory mechanisms for the elevat ed orexigen NPY, the reduction in meal-induced CCK release, and/or a functi onal resistance to 5-HT. (C) 2001 Published by Elsevier Science.