Effects of baclofen on synaptically‐induced cell firing in the rat hippocampal slice

Abstract

1 The effects of baclofen on the synaptically-induced firing of pyramidal and granule cell populations were tested in the rat hippocampal slice. Population spikes were evoked by stimulating excitatory pathways in the presence and absence of bath-applied drug. 2 (±)-Baclofen (20 μM) completely blocked the firing of CA1 or CA3 hippocampal pyramidal cells subsequent to stimulation of projections that originate in area CA3. In contrast, the firing of dentate granule cells evoked by stimulation of the perforant path fibres was depressed by only 46% and baclofen did not affect the monosynaptic firing of CA3 pyramidal cells evoked by mossy fibre stimulation. These results are consistent with the effects of baclofen on the corresponding extracellularly-recorded excitatory postsynaptic potentials (e.p.s.ps). 3 The Schaffer coUateral-commissural population spike in area CA1 was depressed by (−)-baclofen (EC₅₀ = 2.8 μM), GABA (EC₅₀ = 2.2 mM) and 3-aminopropanesulphonic acid (3-APS) (EC₅₀ = 0.34 mM). (−)-Baclofen was 180 times as potent as (+)-baclofen. 4 Bicuculline methiodide (100 μM) did not reverse the depressant action of (−)-baclofen. GABA-induced depressions were antagonized to only a small degree, whilst the effect of 3-APS was readily reversed. Raising the concentration of bicuculline from 100 μM to 500 μM did not further reverse the action of GAB A. 5 The effects of (−)-baclofen and 3-APS on the relationship between extracellular e.p.s.p. and population spike were tested by stimulation of the Schaffer collateral-commissural fibres in area CA1. (−)-Baclofen shifted the ‘input/output’ curve to the right at a concentration of 1 μM, but less or not at all at 3 μM. In contrast, increasing the concentration of 3-APS shifted this curve farther to the right. 6 These results are consistent with the hypothesis that baclofen and GAB A can depress neuronal firing by interacting with a bicuculline-insensitive receptor. In the CA1 area, activation of these receptors mainly depresses transmitter release from terminals of projections from area CA3, but also reduces pyramidal cell excitability.