Biological vulnerability concerning eating disorders can include dysfunction of neurotransmitters such as serotonin, dopamine and norepinephrine that regulate feeding. Studies have shown that all three neurotransmitters, especially serotonergic system, are dysfunctional in eating disorders. Although the satiety-promoting role of the serotonergic system in the control of food intake is well established, there is no current evidence that any selective serotonergic receptor subtype mediates the intake of a specific macronutrient. The role of 5-HT_1A and 5-HT_2C receptor subtypes on food intake and dietary choices was investigated. 20 groups of male Wistar rats, 8 animals each, were intraperitoneal injected 0.05-4.0 mg/kg buspirone (5-HT_1A agonist), 1.0 and 3.0 mg/kg mesulergine (5-HT_2C antagonist with dopaminergic properties), 5.0 and 10.0 mg/kg m-chlorophenylpiperazine (m-CPP) (5-HT_2C/1B agonist) and combinations of mesulergine with buspirone or m-CPP, as well as buspirone with m-CPP at same doses. One group of rats received 1.0 mg/kg apomorphine (dopamine agonist). Animals were given access to a pair of isocaloric diets (protein, PED, or carbohydrate enriched diet, CED) for 4 hours after drug treatment in a food deprivation schedule. Mesulergine caused hyperphagia accompanied by an increase in both PED and CED intake, with CED intake reversed by m-CPP. Busprirone and m-CPP spared protein intake, with an increase and decrease of CED intake consequently. Buspirone due to its action on 5-HT_1A autoreceptors seems to affect diet selection indirectly, since its effect on carbohydrate intake is reversed by m-CPP. 5-HT_2C receptor blockade seems to be the most significant reason for increased carbohydrate consumption, rather than the inhibition of serotonin (5-HT) release through the 5-HT_1A receptors. Our results suggest that both 5-HT_1A and 5-HT_2C receptor subtypes are involved in the protein-sparing effect of 5-HT, while the 5-HT_2C receptors may have the prominent role on 5-HT induced food and carbohydrate intake suppression. These findings extend our understanding on neurobiological substrate of appetite and contribute to the studies related to new drugs against hyperphagia and other eating disorders, especially those referred to 5-HT_2C compounds with agonistic properties.

Key words: Eating disorders, serotonergic system, 5-HT_2C receptors, isocaloric diets, protein, carbohydrate, food deprivation schedule, Wistar rats, buspirone, mesulergine, m-CPP, apomorphine.

S. Antonatos (page 69) - Full article (Greek)