ROLE OF CRH IN THE EFFECTS OF 5-HT-RECEPTOR AGONISTS ON FOOD-INTAKE AND METABOLIC-RATE

Two series of experiments were conducted to investigate the role of co rticotropin-releasing hormone (CRH) in the effects of 5-hydroxytryptam ine (5-HT) on energy intake and energy expenditure. The first set of e xperiments was carried out to confirm the influence of 5-HT1A-, 5-HT1B -, 5-HT2A/2C-receptor agonists on the activation of the hypothalamic-p ituitary-adrenal axis. Plasma corticosterone levels were measured, and a double-immunolabeling procedure was used to deter mine whether the neuronal activity marker, c-Fos protein (Fos), could be found within b rain neurons containing CRH after treatments with 5-HT1A-, 5-HT1B-, 5- HT2A/2C-receptor agonists. The second series of experiments was conduc ted to assess the involvement of CRH in the effects of 5-HT on food in take and metabolic rate (VO2). The effects of the 5-HT1A-, 5-HT1B-, 5- HT2A/2C-receptor agonists on food intake and VO2 were measured in rats treated with the CRH antagonist, alpha-helical CRH-(9-41). In both ex periments rats were intraperitoneally injected with either a vehicle ( NaCl 0.9%), the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n-propyl amino) tetralin hydrobromide (8-OH-DPAT), the 5-HT1B-receptor agonist thoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU-24969 ), or the 5-HT2A/2C-receptor agonist +/-)-1-(2,5-dimethoxy-4-iodopheny l)-2-aminopropane HCl (DOI). Fos immunoreactivity was detectable withi n the CRH-containing neurons of the paraventricular nucleus of the hyp othalamus (PVH) after injection of each of the 5-HT-receptor agonists used. The CRH antagonist alpha-helical CRH-(9-41) attenuated the incre ases in metabolic rate induced by DOI and 8-OH-DPAT, alpha-Helical CRH did not, however, prevent the effects of RU-24969 and DOI on either n octurnal metabolic rate or food intake. The present results provide fu rther evidence for a role of CRH in 5-HT-mediated thermogenic effect, which likely involves the 5-HT2A/2C receptor during the day and the 5- HT1A receptor during the night. Moreover, these results do not support a role for CRH in 5-HT anorectic effects, which likely involves 5-HT1 B and 5-HT2A/2C receptors. Finally, the results of this study indicate that the stimulation of CRH-containing neurons located in the PVH doe s not necessarily predict changes in food intake and energy expenditur e.