Changes in Fos expression in various brain regions during deoxycorticosterone acetate treatment: relation to salt appetite, vasopressin mRNA and the mineralocorticoid receptor.
Salt appetite, a conditioning factor for hypertension and cardiovascular diseases, is produced when high doses of mineralocorticoids are given to experimental animals. A commonly used procedure to identify neuronal activation is to determine the number of Fos-immunoreactive cells. In rats with established salt appetite after 8 days of deoxycorticosterone acetate (DOCA) treatment, Fos-positive cells were studied in seven brain areas. Significant increases in Fos activity were recorded in the paraventricular (PVN) and supraoptic (SON) nuclei, median preoptic nucleus (MnPO), organum vasculosum of the lamina terminalis (OVLT), preoptic area (POA), bed nucleus of the stria terminalis (BNST) and amygdala (AMYG). In most of these areas, increased Fos expression was also observed early (2 h) after a single DOCA injection, well before salt appetite develops. Using a mineralocorticoid receptor (MR) antibody, we studied whether Fos-active regions also expressed MR. MR-positive cells were found in the OVLT, MnPO, AMYG and BNST, but not in the POA, PVN and SON. In the PVN and SON, nevertheless, prolonged or single DOCA treatment increased expression of mRNA for arginine vasopressin (AVP). The present demonstration of Fos activation, in conjunction with differential expression of MR and stimulation of AVP mRNA, suggests that a neuroanatomical pathway comprising the AMYG, osmosensitive brain regions and magnocellular nuclei becomes activated during DOCA effects on salt appetite. It is recognized, however, that DOCA effects may also depend on mechanisms and brain structures other than those considered in the present investigation. Since some Fos-positive regions were devoid of MR, a comprehensive view of DOCA-induced salt appetite should consider nongenomic pathways of steroid action, including the role of reduced DOC metabolites binding to GABAergic membrane receptors.
Pietranera
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L
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental and Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Saravia
F E
FE
McEwen
B S
BS
Lucas
L L
LL
Johnson
A K
AK
De Nicola
A F
AF
D000818:Animals; D001066:Appetite / Q000502:physiology*; D001127:Arginine Vasopressin / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012965:Sodium Chloride; D014018:Tissue Distribution
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D001127:Arginine Vasopressin; D003900:Desoxycorticosterone; D012965:Sodium Chloride