Abstract
It has been suggested that central serotonin is anorexigenic and this action is mediated, at least in part, by 5-HT2A/C receptors and activation of POMC neurons. This study examined the systemic effects of 5-HT2A/C receptor agonist on food intake, body weight and blood glucose levels in Zucker fatty rats in which leptin receptor is impaired. Fatty rats were intraperitoneally (i.p.) administered with a 5-HT2A/C agonist DOI at 1.0 mg/kg (n=4) or saline (n=4) from 7 to 10 weeks of age, and food intake, body weight and blood glucose levels were measured. Control Lean rats received the same treatment. In long term measurements, daily food intake and weight gain in Fatty rats were significantly decreased in DOI group as compared to control group. In Lean rats, neither food intake nor weight gain was significantly different between DOI and control groups. There were no difference in blood glucose levels between DOI and control groups both in Fatty and Lean rats. In Fatty rats, upon termination of i.p. DOI food intake was temporarily increased, however weight did not change significantly, indicative of increased energy consumption. In short term measurements, food intake was reduced at 1-2.5 hrs after i.p. DOI in Fatty but not Lean rats, and blood glucose level was lowered at 0.5-3 hrs both in Fatty and Lean rats. These results indicate that activation of 5-HT2A/C restricts feeding and ameliorates obesity in Fatty rats and that some of these effects may be produced by restoring the downstream signaling pathway of the leptin receptor impaired in Fatty rats. [J Physiol Sci. 2006;56 Suppl:S226]
