期刊
NEUROPHARMACOLOGY
卷 39, 期 1, 页码 65-74出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(99)00075-1
关键词
GABA; anticonvulsant; vigabatrin; inhibition; paired-pulse; IPSPs
The antiepileptic drug, gamma-vinyl GABA (GVG, vigabatrin), is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for the breakdown of GABA. In hippocampal slices prepared from rats pretreated with either an anticonvulsant dose of GVG (1500 mg/kg) or saline, electrophysiological recordings were performed in order to examine the effects of GVG pretreatment on GABAergic neurotransmission. Although GVG had no effect on the effectiveness of GABA-mediated inhibition when elicited by a single stimulus, it reversed the activity-dependent depression of inhibition which is typically observed when inhibitory pathways are activated repetitively by a train of stimuli delivered at low frequency. Similarly, GVG pretreatment prevented the progressive decline in the amplitude of monosynaptic inhibitory postsynaptic potentials (IPSPs) during low-frequency stimulation of inhibitory interneurons. Thus, in slices from GVG pretreated rats, the amplitudes of both the fast and slow components of the last of a series of IPSPs evoked by a 5 Hz, 4 s train were maintained at 91.5 +/- 6.6% and 87.7 +/- 6.5%, respectively, compared to 61.1 +/- 3.9% and 57.1 +/- 5.0% in control slices. Finally, in slices from GVG pretreated rats, we observed a reduction in the ability of the GABA, receptor agonist, baclofen, to decrease the amplitude of monosynaptic inhibitory postsynaptic currents. These results suggest that GVG may produce its frequency-dependent actions by reducing the function of release regulating presynaptic GABA(B), autoreceptors. The frequency-dependent reinforcement of inhibition by GVG may importantly contribute to the anticonvulsant effectiveness of this compound. (C) 1999 Elsevier Science Ltd. All rights reserved.
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