Immunocytochemical localization in rat brain of the enzyme that synthesizes ?-hydroxybutyric acid.

?-Hydroxybutyric acid, a reductive catabolite of GABA, has numerous neuropharmacological and neurophysiological properties when injected systematically to animals. Recently, a specific succinic semialdehyde reductase (SSR2) has been isolated from rat brain. This enzyme specifically produces [(3)H]?-hydroxybutyrate from [(3)H]GABA when incubated in vitro with rat brain tissue slices. A specific antibody against this enzyme has been raised in the rabbit and employed to localize by immunocytochemical procedures the sites of ?-hydroxybutyrate synthesis in two regions of rat brain, the nucleus Raphe dorsalis and the median hypothalamus. Light microscopy reveals the presence of numerous SSR2-positive reactions in the cytoplasm of fusiform or ovoid cells. High magnification shows that only neurons of varous sizes are stained; the cytoplasm is uniformly labelled with a few punctate deposits. At the electron microscopic level, some staining appears in the somata of neurons and in fibres or axonal terminals.