Journal of Neuroscience, Vol 2, 698-703, Copyright © 1982 by Society for Neuroscience
The blocking action of baclofen on excitatory transmission in the rat hippocampal slice
HR Olpe, M Baudry, L Fagni and G Lynch
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.