Phaclofen has recently been described as an antagonist to baclofen at both peripheral and central receptors. We have applied phaclofen in known concentrations to an isolated rat brain slice preparation containing the septal nuclei. Our data demonstrate that phaclofen antagonizes responses to exogenously applied baclofen in a competitive manner. On the other hand, phaclofen is not as effective in antagonizing competitively the synaptically mediated late hyperpolarizing response (LHP) recorded from the same or similar dorsolateral septal nucleus (DLSN) neurons from which baclofen responses were recorded. Our data support the usefulness of phaclofen as a competitive antagonist of baclofen, and suggest that when larger stimulus intensities are applied, the LHP in the dorsolateral septum of the rat may be mediated by a transmitter in addition to gamma-aminobutyric acid (GABA).
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