Role of crh in the effects of 5-ht-receptor agonists on food intake
and metabolic rate.
Bovetto, Sylvie, Claude Rouillard, and Denis Richard.
D[acute]epartement de Physiologie, Facult[acute]e de
M[acute]edecine, Universit[acute]e Laval, D[acute]epartement de
Pharmacologie et Centre de Recherche en Neurobiologie,
H[circumflex]opital de l'Enfant-J[acute]esus, Qu[acute]ebec, G1K 7P4
(Canada)
APStracts 3:0180R, 1996.
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-HT 1a-, 1b-, 2a/2c-receptor agonists on the activation of the HPA
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-HT 1A-, 1B-, 2A/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 VO2 (metabolic rate). The effects of the 5-HT 1A-, 1B-, 2A/2C
-receptor agonists on food intake and metabolic rate 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-HT 1A-receptor agonist (+/-)-8-hydroxy
-dipropylaminotetralin hydrobromide (8-OH-DPAT), the 5-HT 1B-receptor
agonist 5-methoxy 3 (1,2,3,6-tetrahydro 4 pyridinyl)-1H-indole
succinate (RU-24969) or the 5-HT 2A/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) following
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 5-HT 2A/2C receptor during the day and
the 5-HT 1A receptor during the night. Moreover, these results do not
support a role for CRH in 5-HT anorectic effects, which likely
involves 5-HT 1B and 5HT 2A/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.
Received 16 August 1995; accepted in final form 3 May 1996.
APS Manuscript Number R510-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96