The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

Abstract

gamma-Butyrolactone (GBL) and its hydrolysate, gamma-hydroxybutyrate (GHB) have been known to distribute physiologically in the brain (1) -7) have suggested that the central action of GHB is rather excitatory than inhibitory, because GHB causes catatonia-like or hallu cinogenic state and even grand mal seizures by large doses in cats. The problems here are whether both GBL and GHB have excitatory central effects, and whether the effects depend on the species difference by which the central action varies..The comparison of behavioral effects of GBL and GHB among mice, rats and rabbits in the present experiments demontrated more central inhibitory nature of GBL than GHB as well as some signes of central excitement by both drugs. In addition, the possible mechanism of central excitement by GBL in rabbits was discussed electroencephalogra phically in relation to the similar effects of pentobarbital sodium and pentylenetetrazol. METHODSThe animals used were about 500 dd-strain mice of either sex, 30 male rats of Wistar strain and about 50 albino rabbits of either sex. They except mice were housed in an individual cage allowing free access to a commercial diet and water at the room tempera ture of 22--!-2°C.GBL and sodium salt of GHB were kindly supplied from Ono Pharmaceutical Co.,Osaka. The drugs dissolved in saline were injected to mice and rats intraperitoneally in volume of 0.1 ml/10 g body weight. In the rabbis, 10 to 20% solution of either drug was injected into the marginal ear vein at the rate of 1 to 2 ml/min. Thereafter, the changes in spontaneous behaviors, reflex activities and responses to grasping the animal body, tail pinch and skin scratching were observed at least for 6 hours after the drug