Effects of acetaldehyde on c-fos mRNA induction in the paraventricular nucleus following ethanol administration.
OBJECTIVE
The effect of acetaldehyde on c-fos mRNA expression in the paraventricular nucleus (PVN) of the rat was examined using in situ hybridization histochemistry.


METHODS
Increases in acetaldehyde concentrations were induced using cyanamide (a potent inhibitor of aldehyde dehydrogenase), in the presence of two different doses of ethanol. Concentrations of blood ethanol and acetaldehyde were determined by head space gas chromatography.


RESULTS
Neither cyanamide alone nor the low dose of ethanol (1 g/kg) alone increased c-fos expression in the PVN. However, the combination of cyanamide and low dose ethanol resulted in a significant and maximal increase in c-fos mRNA in the PVN. High dose ethanol (3 g/kg) resulted in a significant increase in c-fos mRNA. This stimulation also appeared maximal as there was no further increase in c-fos expression in the presence of cyanamide.


CONCLUSIONS
These data suggest that acetaldehyde accumulation in blood has an important stimulatory effect on c-fos expression in the PVN at low ethanol concentrations. Furthermore, this stimulation of c-fos mRNA appears to be an either/or response: not activated in response to low dose ethanol, but maximally to high dose ethanol. These data also provide further evidence for a dissociation between the activation of c-fos and corticotrophin-releasing factor (CRF) mRNA in the PVN, as we have previously demonstrated that this dose of cyanamide alone is sufficient to evoke a sustained increase in plasma corticosterone and an increase in CRF mRNA.
Kinoshita
Hiroshi
H
Department of Legal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Jessop
David S
DS
Roberts
David J
DJ
Ameno
Kiyoshi
K
Ijiri
Iwao
I
Hishida
Shigeru
S
Harbuz
Michael S
MS
D000079:Acetaldehyde / Q000097:blood*; D000818:Animals; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D000431:Ethanol; D000079:Acetaldehyde