The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

Abstract

The biphasic mode of action of gamma-butyrolactone (GBL) and ,gamma-hydroxybuty rate (GHB) in the central nervous system has been confirmed in the previous report (1) . The former compound elevates the reticular arousal stimulation threshold for the mani festation of the hippocampal theta waves without significantly affecting the increased mani festation of the fast waves in the rabbit's EEG. At the same time , the thalamic recruit ing response is usually depressed or sometimes is slightly augmented . In order to observe the mode of action on the brain structures more in detail, the effects of both compounds on the cortical dendritic responses (DR) caused by the electrical stimulation of the corti cal surface are studied in the cats.The small doses of GHB augment the DR , while the large doses inhibit it. Based on the obtained results the dose-response relationship of GHB and its related compounds is discussed. On the other hand, GBL proved to be inactive in this respect . Correla tion of the effects between GHB and gamma-aminobutyric acid (GABA) , the latter of which is now accepted as the inhibitory transmitter in the several parts of the central nervous system, is also investigated. Roth et al. (2, 3) have already postulated that GHB is the pharmacologically active metabolite derived from gamma-butyrolactone in the body. METHODSFemale or male cats weighing 1.8 to 4 .2 kg were anesthetized with ether inhalation or with intraperitoneal injection of 40 to 50 mg/kg of o-chloralose or 30 mg/kg of pento barbital sodium. After the tracheal intubation the anesthetized cats with ether were made as encephale isole preparation and were maintained on the artificial respiration . All the anesthetized animals were fixed of their heads on the stereotaxic instrument of Todai-Noken type. The contact surface of the animal body with frame bars of the instrument was , when required, anesthetized with the topical application of xylocaine hydrochloride . Constant level of the nnecthee;a wnwac attn;nvr1 1-.v the S7unnlementnrv inieetinn of nentnl.a, h;tal nr