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-hydroxydipropylaminote tralin hydrobromide (8-OH-DPAT), RU-24969, +/-)-1-(2,5-dimethoxy-4-iod ophenyl)-2-aminopropane hydrochloride (DOI), and 1-phenylbiguanide wer e administered to male Wistar rats to assess the respective involvemen t 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 w ere carried out, each series addressing the effects of four doses (inc luding saline or dose 0) of each of the agonists selected. The drugs w ere intraperitoneally injected in spontaneously fed animals. Injection s 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 me asurements were carried out over the 12-h periods ensuing after the ag onist injections. The two highest doses of the 5-HT1A- receptor agonis t 8-OH-DPAT led to a quickly appearing but transient elevation of diur nal VO2. During the night, VO2 was higher when the rats were treated w ith 8-OH-DPAT than when they were treated with saline. There was no si gnificant effect of 8-OH-DPAT on either diurnal or nocturnal food inta ke. The highest dose of RU-24969 induced a significant increase in diu rnal 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 noc turnal hypophagia. The 5-HT2A/2C-receptor agonist DOI produced an incr ease in diurnal VO2, but similar to RU-24969 it attenuated the elevati on of nocturnal metabolic rate. DOI elicited a clear nocturnal hypopha gia, whereas it was without significant effect on diurnal food intake. The 5-HT3-receptor agonist 1-phenylbiguanide did not modify either VO 2 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-HT 1B, and 5-HT2 in the control of energy expenditure in rats.