EFFECTS OF ACETALDEHYDE ON c-fos mRNA INDUCTION IN THE PARAVENTRICULAR NUCLEUS FOLLOWING ETHANOL ADMINISTRATION

— Aims: 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.