The blocking action of baclofen on excitatory transmission in the rat hippocampal slice.
The mode of action of baclofen on the physiology of the rat hippocampus was investigated by studying its effect on electrophysiological responses in the hippocampal slice preparation and by measuring biochemical parameters related to glutamate uptake, binding, and release. Baclofen inhibited, in a dose-dependent fashion, the dendritic field potentials in field CA1 produced by stimulation of the Schaffer commissural fiber system. The drug was inactive in this respect at concentrations of 10 and 100 nM but consistently reduced the amplitude of both the dendritic field potential and the population spike at a concentration of 1 microM. At a concentration of 25 microM, baclofen virtually abolished the dendritic and cell body responses to afferent stimulation. Recovery of field potentials required between 7 and 10 min following the addition of 1 microM baclofen. The levorotatory form of baclofen was much more potent in suppressing synaptic responses than was the dextrorotatory enantiomer. Baclofen, at a concentration of 5 microM, strongly antagonized the excitation of pyramidal neurons evoked by iontophoretically applied glutamate. The antagonism of the glutamate effect was much reduced when the slices were maintained in low calcium, high magnesium perfusion medium. Moreover, under low calcium conditions, baclofen did not interfere with the effects of bath-applied glutamate on antidromically elicited responses. Baclofen did not affect the Na+-dependent or Na+-independent binding of [3H]glutamate to crude synaptic membrane fractions from the hippocampus. However, at a concentration of 1 microM, it markedly inhibited potassium-induced release of [3H]glutamate from hippocampal synaptosomes. Taken together, the present results strongly suggest that baclofen suppresses synaptic responses in the Schaffer commissural fiber system of the hippocampus by blocking the release of an excitatory amino acid transmitter.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D046508:Culture Techniques; D003712:Dendrites / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D001418:Baclofen