Effect of 5-HT1A receptor activation on hypothalamic glucose

The somatodendritic 5-HT1A agonist 8-OH-DPAT reduces serotonergic activity and stimulates feeding in freely feeding rats. Interactions between circulating glucose and 5-HT1A receptor expression related to feeding have been described. The aim of the present microdialysis study was to (1) describe the relation between feeding and glucose in the LH, (2) to investigate if peripherally administered 8-OH-DPAT itself has an effect on extracellular glucose in the lateral hypothalamus (LH) of conscious rats. Baseline glucose concentrations were significantly different in microdialysis samples obtained from food deprived rats compared to freely feeding rats. After re-feeding, a significant rise in glucose levels by 45% was observed in the formerly food deprived rats. In freely feeding rats, 8-OH-DPAT (0.3 mg/kg, i.p.) reduced glucose level in the LH significantly. The effect of 8-OH-DPAT on brain glucose was antagonized by pre-treatment with the 5-HT1A antagonist WAY 100635 (3 mg/kg i.p.) which had no effect on its own. The data indicate, therefore, that the effect of 8-OH-DPAT on hypothalamic glucose is mediated by 5-HT1A receptors. In contrast, the same dose of 8-OH-DPAT proven effective in the brain had no effect on peripheral glucose. Only a very high dose of the 5-HT1A agonist (1.8 mg/kg i.p.) had a hyperglycaemic effect in the periphery. In conclusion, the present results show for the first time, that glucose in the lateral hypothalamus increases with a meal. The data demonstrate furthermore 8-OH-DPAT-induced changes of hypothalamic glucose level, implicating 5-HT1A receptors being involved not only in the control of hypothalamic 5-HT as shown before, but also in the control of hypothalamic glucose.