Identification of endogenous gamma-hydroxybutyrate in human and bovine brain and its regional distribution in human, guinea pig and rhesus monkey brain.

Gamma-Hydroxybutyric acid (GHB), a compound that has interesting neuropharmacological actions when administered systemically, was shown by means of gas chromatography-mass spectrometry to be present in postmortem samples of human brain in concentrations ranging from 2 to 20 nmol/g. Tissue samples from the basal ganglia contained 2 to 3 times as much GHB as tissue samples from cortical regions. The regional brain distribution of GHB was examined in the guinea pig and rhesus monkey and found to parallel the distribution observed in human brain. The levels of GHB found in the regional areas of human and monkey brain investigated were higher than the levels found in similar regions of guinea-pig brain. Additional studies demonstrated that there is a slow postmortem increase (about 2-fold) in the endogenous levels of GHB in bovine caudate and guinea-pig brain which is maximal about 6 hr postmortem. This postmortem increase could in part explain the higher levels of GHB found in human brain. However, postmortem changes could not account for the large differences observed in the levels of GHB found in bovine caudate and those found in guinea-pig, monkey and human caudate. Only traces of GHB could be detected in human blood and cerebrospinal fluid.