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The present study describes the role of 5-HT1A receptors in the serotonergic control of food intake in obese Zucker rats of different ages. In addition, serotonin (5-HT) and cholecystokinin (CCK) content and 5-HT turnover were determined in various brain regions. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 100 microg/kg) stimulated food intake in 3-month-old lean control rats but inhibited feeding in obese Zucker rats (300 microg/kg). This pattern remained the same in 6-month-old rats. At 10 months of age, 8-OH-DPAT lost its inhibitory activity in the obese rats but still stimulated feeding in lean controls (300 microg/kg). 5-HT levels were higher in the hypothalamus and in the frontal and parietal cortices of 3-month-old obese Zucker rats and were associated with a lower cortical turnover. In the parietal cortex and the hypothalamus of 6-month-old rats, 5-HT levels were still higher, linked with a lower hypothalamic turnover. No differences were observed in 10-month-old rats. CCK content was not different between obese Zucker rats and lean rats. The persistently different feeding responses to 8-OH-DPAT in obese Zucker rats and lean controls may be related to changes in brain 5-HT metabolism in the obese Zucker rats.