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 corticotropin-releasing hormone (CRH) in the effects of 5-hydroxytryptamine (5-HT) on energy intake and energy expenditure. The first set of experiments was carried out to confirm the influence of 5-HT1A-, 5-HT1B-, 5-HT2A/2C-receptor agonists on the activation of the hypothalamic-pituitary-adrenal axis. Plasma corticosterone levels were measured, and a double-immunolabeling procedure was used to determine whether the neuronal activity marker, c-Fos protein (Fos), could be found within brain neurons containing CRH after treatments with 5-HT1A-, 5-HT1B-, 5-HT2A/2C-receptor agonists. The second series of experiments was conducted to assess the involvement of CRH in the effects of 5-HT on food intake 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 experiments rats were intraperitoneally injected with either a vehicle (NaCl 0.9%), the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), the 5-HT1B-receptor agonist 5-methoxy-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-iodophenyl)-2-aminopropane HCl (DOI). Fos immunoreactivity was detectable within the CRH-containing neurons of the paraventricular nucleus of the hypothalamus (PVH) after injection of each of the 5-HT-receptor agonists used. The CRH antagonist alpha-helical CRH-(9-41) attenuated the increases 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 nocturnal metabolic rate or food intake. The present results provide further 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-HT1B and 5-HT2A/2C receptors. Finally, the results of this study indicate that the stimulation of CRH-containing neurons located in the PVH does not necessarily predict changes in food intake and energy expenditure.
Bovetto
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S
Départment de Physiologie, Faculté de Médecine, Université Laval, Québec, Canada.
Rouillard
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C
Richard
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D
D000818:Animals; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D004435:Eating / Q000187:drug effects*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone