BACLOFEN SELECTIVELY INHIBITS TRANSMISSION AT SYNAPSES MADE BY AXONS OF CA3 PYRAMIDAL CELLS IN THE HIPPOCAMPAL SLICE

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (2) , 291-297
Abstract
The effects of baclofen, an antispastic drug, on excitatory transmission were tested (in rats) by bath application to the hippocampal slice preparation. (.+-.)-Baclofen (20 .mu.M) strongly depressed extracellularly recorded synaptic responses to stimulation of projections that originate from CA3 hippocampal pyramidal cells. Responses to stimulation of 4 other excitatory pathways were little affected and the amplitudes of presynaptic fiber potentials and antidromic responses were unaltered. When tested on the Schaffer collateral-commissural-CA1 pyramidal cell synapse, (.sbd.)-baclofen depressed the amplitude of the extracellular excitatory postsynaptic potential with an IC50 [median inhibitory concentration] of 3.7 .mu.M and was 180 times more potent than (+)-baclofen. GABA, 3-aminopropanesulfonic acid and imidazole-4-acetic acid also inhibited transmission at this site. Baclofen could suppress the response completely, and its action was unaffected by bicuculline. Imidazole-4-acetic acid could suppress the response by a maximum of only 75%, and its action was highly sensitive to bicuculline. GABA and 3-aminopropanesulfonic acid could suppress the response completely, and their actions were relatively weakly antagonized by bicuculline. Baclofen apparently inhibits excitatory transmission by interacting with a bicuculline-insensitive GABA receptor. These receptors may be located on 1 type of glutamatergic/aspartergic synaptic terminal, exemplified by axon terminals of CA3 hippocampal pyramidal cells. Synapses made by these axons may serve as models for studying the mechanism of action of baclofen.