The osmotic component of ethanol and urea action is critical for their immediate stimulation of thyrotropin-releasing hormone (TRH) release from rat brain septum

There is considerable evidence linking alcohol consumption and sedation and TRH in the brain septum. Moreover, innate septal TRH concentration is inve rsely related to the degree of ethanol preference. Recently we demonstrated in rats that four-week ethanol drinking increased the septal TRH content b y 50 %. We had shown previously that ethanol induces neuronal swelling, whi ch is known to evoke the secretion of hormones, peptides and amino acids fr om various types of cells. We have therefore explored the effect of hyposmo tic medium and of 80 and 160 mM ethanol and 80 mM urea (both permeant molec ules) in isosmotic and hyperosmotic (preventing cell swelling) media on the in vitro release of TRH by the rat septum. Lowering medium osmolarity resu lted in a hyposmolarity-related increase in TRH secretion. Both ethanol and urea stimulated TRH release only in isosmolar solution. Our data indicate that ethanol in clinically relevant concentrations can induce TRH release f rom the septum by a mechanism involving neuronal swelling.