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 noctural 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of chronic treatment with 5-HT1 agonist (8-OH-DPAT and RU 24969) and antagonist (isapirone) drugs on the behavioural responses of mice to 5-HT1 and 5-HT2 agonists