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.
Jhanwar-Uniyal
M
M
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
Moorjani
B
B
Kahn
A H
AH
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D004040:Dietary Carbohydrates; D004334:Drug Administration Schedule; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D014044:Tolbutamide / Q000494:pharmacology*
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014044:Tolbutamide