S. Bovetto et al., ROLE OF CRH IN THE EFFECTS OF 5-HT-RECEPTOR AGONISTS ON FOOD-INTAKE AND METABOLIC-RATE, American journal of physiology. Regulatory, integrative and comparative physiology, 40(5), 1996, pp. 1231-1238
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.