FUNCTIONAL ASSESSMENT OF THE 5-HT 1A-RECEPTOR, 1B-RECEPTOR, 2A/2C-RECEPTOR, AND 3-RECEPTOR SUBTYPES ON FOOD-INTAKE AND METABOLIC-RATE IN RATS

The 5-hydroxytryptamine (5-HT) agonists (+/-)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), RU-24969, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), and 1-phenylbiguanide were administered to male Wistar rats to assess the respective involvement of the 5-HT 1A-, 1B-, 2A/2C-, and 3-receptor subtypes in the control of food intake and metabolic rate (VO2). Four series of experiments were carried out, each series addressing the effects of four doses (including saline or dose 0) of each of the agonists selected. The drugs were intraperitoneally injected in spontaneously fed animals. Injections were performed during the first 15 min of either the diurnal or the nocturnal phases of the light-dark daily cycle. Food intake and VO2 measurements were carried out over the 12-h periods ensuing after the agonist injections. The two highest doses of the 5-HT1A- receptor agonist 8-OH-DPAT led to a quickly appearing but transient elevation of diurnal VO2. During the night, VO2 was higher when the rats were treated with 8-OH-DPAT than when they were treated with saline. There was no significant effect of 8-OH-DPAT on either diurnal or nocturnal food intake. The highest dose of RU-24969 induced a significant increase in diurnal VO2, whereas all doses of RU-24969 blunted the nocturnal rise in metabolic rate characteristically observed in rats kept under a daily light-dark cycle. Importantly, RU-24969 induced marked diurnal and nocturnal hypophagia. The 5-HT2A/2C-receptor agonist DOI produced an increase in diurnal VO2, but similar to RU-24969 it attenuated the elevation of nocturnal metabolic rate. DOI elicited a clear nocturnal hypophagia, whereas it was without significant effect on diurnal food intake. The 5-HT3-receptor agonist 1-phenylbiguanide did not modify either VO2 or food intake within the range of the doses tested. In conclusion, the results of this study emphasize the involvement of the 5-HT1B and 5-HT2 receptors in the control of food intake and that of 5-HT1A, 5-HT1B, and 5-HT2 in the control of energy expenditure in rats.