Indications of pre- and post-synaptic 5-HT1A receptor interactions in feeding behavior and neuroendocrine regulation.

This bipartite study uses behavioral and biochemical means to explore the involvement of both pre- and post-synaptic 5-HT1A receptors in the control of food intake and neuroendocrine regulation. In the pharmacological study, the administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 60 micrograms/kg b.wt., i.p.) to rats caused a significant increase in 2 h intake of a high carbohydrate (CARB)/sugar diet (P < 0.05) during the relatively inactive feeding period of the late light cycle. No significant change was detected in the intake of Purina laboratory chow at 2 h, or of the intake of either diet at 4 h and 24 h after 8-OH-DPAT administration. Injection of 8-OH-DPAT induced a drop in insulin levels in rats maintained on high CARB/sugar diets only (-90%; P < 0.05). It also caused an increase in circulating glucose levels in both high CARB/sugar (240%; P < 0.01) and chow fed (123%; P < 0.05) rats; it did so more intensely in high CARB/sugar-fed rats. In the biochemical study, radioligand binding techniques were used to assess 5-HT1A receptor density in the hypothalamus, as well as the relationship between 5-HT1A receptors and circulating levels of insulin and glucose. Chronic and acute administration (25 mg/kg b.wt./5 injections, and 50 mg/kg b.wt., respectively, i.p.) of the potent hypoglycemic agent tolbutamide (TOL) caused a significant increase in 5-HT1A receptor density (+243% and +132.6%, respectively; P < 0.05) in the medial hypothalamus but not in the lateral hypothalamus, as compared to vehicle-treated rats. Chronic glucose replacement therapy showed a trend towards reversing the depressed circulating glucose levels as well as the medial hypothalamic 5-HT1A receptor density to control levels. These studies indicate that the pre-synaptic mechanism of 8-OH-DPAT-induced hyperphagia may require specific circulating levels of insulin and glucose, which are regulated via post-synaptic 5-HT1A receptors.