A 5-HT_(1A) Antagonist May Enhance the Anorectic Effect of A 5-HT_(2c) Receptor Agonist

摘要

Direct or indirect stimulation of serotonin receptors (5-HT2cR), 5-HTIBR and 5-HT6R subtypes decrease food intake while stimulation of 5-HT_(2C)R increases it. Using nonselective drugs or increasing 5-HT at the synaptic cleft may bind to different subtypes producing opposing effects on intake, if this would be the case, agonist action at 5-HT_(1A)R may obscure the anorectic effect. We tested the hypothesis that indorenate (INDO) an agonist with low affinity for 5-HT_(1B/2C)Rs that decreases food intake, but also with high affinity for 5-HT_(1A)R, may benefit from the blockade of 5-HT_(1A)R to clearly express its anorectic action. Male Wistar rats were trained to eat their food and water daily in a period of 4 h. On test days mesulergide (non-selective 5-HT2c/2A antagonist, 1.0 mg/kg), mianserin (non-selective 5-HT_(2A/2B/2C) antagonist, 3.0 mg/kg), methiothepin (non-selective 5-HT_(1E/1F/1A) antagonist, 0.3 mg/kg) or saline were given before INDO (17.0 mg/kg); a control group received two injections of saline. INDO decreased food intake; mesulergide and mianserin prevented its anorectic effect, although only the antagonism of mesulergide reached statistical significance. Methiothepin enhanced the anorectic effect of INDO. Blockade of 5-HT_(1A)R allowed the observation of the full participation of the 5-HT_(2C)R on the anorectic action of INDO.