-HYDROXYBUTYRATE-INDUCED INCREASE IN BRAIN DOPAMINE: LOCALIZATION BY FLUORESCENCE MICROSCOPY

¹ Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut

The central nervous system depressant compound -hydroxybutyric acid and its precursor, -butyrolactone are known to produce a selective increase in the concentration of brain dopamine. The fluorescence histochemical method was employed to determine the cellular localization of dopamine in rat brain after its concentration was elevated by the administration of -butyrolactone. The lactone is rapidly converted to -hydroxybutyrate in the body, and the latter is responsible for the observed rise in brain dopamine. In controls, a diffuse background fluorescence was observed in areas of the brain ( e.g., caudate nucleus, accumbens nucleus and olfactory tubercle) that are known to have high dopamine content. After -butyrolactone was given, brillantly fluorescent " dots" or " varicosities" 0.5 to 1.0 µ in diameter were seen throughout these same areas. In contrast, a monoamine oxidase inhibitor, pargyline, which also increases brain dopamine ( but not selectively) merely enhances and extends the diffuse fluorescence as seen in controls. It is concluded that -butyrolactone or -hydroxybutyrate produce a selective increase in dopamine concentration at highly localized sites presumed to represent the nerve endings or terminals of the dopamine-containing neurons.