| Summary: | 碩士 === 臺灣大學 === 藥理學研究所 === 95 === Gamma-Hydroxybutyrate acid (GHB) is a compound structurally similar to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). As GHB has the ability to induce sleep in humans, it was approved in 2002 by the U.S Food and Drug Administration (FDA) to treat narcolepsy. Previous publications have used this drug in alcohol addiction studies since GHB is believed to relieve withdrawal symptoms. Despite this beneficial application of GHB, it is an abused club drug that is often used in date rape cases. Due to the considerable abusive potential of GHB, it is classified as a Schedule I controlled substance in the United States, and is a Schedule II controlled substance in Taiwan. Long term use of GHB can lead to dependence, while multiple studies have reported its toxic effects in central nervous system. Although there is speculation that GHB causes amnesia, the underlying cellular mechanism(s) remain unclear. Therefore, this study investigates the effect of GHB on basal synaptic transmission and synaptic plasticity of field excitatory post synaptic potentials (fEPSP) at the Schaffer collateral–CA1 synapse of mouse brain hippocampus slices using an extracellular recording technique.
In the basal synaptic transmission study, we used mice from two different age groups to evaluate the effect of GHB on fEPSP amplitudes evoked by a basal stimulation of 0.05Hz. In both groups, the lowest (0.3~1 micro molar) and highest (10 micro molar) GHB concentrations caused an increase and an obvious strong decrease of fEPSP amplitudes, respectively. At moderate concentrations (3 micro molar), there seemed to be a bi-directional effect on the fEPSP amplitudes; the increased effect was statistically significant while the decreased effect was not. In addition, 10 micro molar of the GHB receptor antagonist NCS-382 seemed to antagonize the effect of GHB, yet this could not be confirmed statistically due to an insufficient sample size. Interestingly, NCS-382 augmented the inhibitory effect of GHB in four slices.
GHB (10 micro molar) was applied on six to eight week old murine hippocampus slices to evaluate synaptic plasticity at the Schaffer collateral–CA1 synapse. Long term depotentiation (LTP) was accomplished by using stimuli of three trains (with a 15 second interval) of 10 theta burst (100Hz for 0.04Hz); long term depression (LTD) and depotentiation were induced with a 1Hz stimulus for 15 minutes.
Application of GHB (10 micro molar) had a negative effect on LTP and post titanic potentiation (PTP) with little significance; whereas there was a notably enhanced depotentiation but LTD was not affected. NCS-382 (10
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