Phaclofen‐insensitive presynaptic inhibitory action of (±)‐baclofen in neonatal rat motoneurones in vitro

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Abstract
1 Intracellular recordings were made from antidromically identified motoneurones in transverse spinal cord slices from neonatal (12–16 day) rats. 2 Superfusion of (±)-baclofen (0.5–50 μm) reduced the excitatory postsynaptic potentials (e.p.s.ps) and inhibitory postsynaptic potentials (i.p.s.ps) evoked by dorsal root or dorsal root entry zone stimulation in a concentration-dependent manner; the calculated EC50 was 2.4 μm. Baclofen in comparable concentrations also reversibly eliminated spontaneously occurring e.p.s.ps and i.p.s.ps. 3 (−)-Baclofen was more effective as compared to baclofen in reducing the synaptic responses, whereas (+)-baclofen at concentrations as high as 50 μm was ineffective. 4 Baclofen (< 5 μm) attenuated the synaptic responses without causing a significant change of passive membrane properties and depolarizations induced by exogenously applied glutamate. In addition to synaptic depression, baclofen (> 5 μm) caused a hyperpolarization associated with decreased membrane resistance in some of the motoneurones; the glutamate responses were also attenuated. 5 Baclofen reversibly depressed the spike after-hyperpolarization of the motoneurones. 6 GABA (1–10 mm) depressed synaptic transmission and depolarized or hyperpolarized motoneurones. While potentiated by the uptake inhibitor nipecotic acid, the synaptic depressant effect of GABA was not antagonized by bicuculline. 7 The synaptic depressant effect of baclofen was neither blocked by GABAA antagonists bicuculline and picrotoxin (10–50 μm) nor by the GABAB antagonist phaclofen (0.1–1 mm). 8 It is suggested that baclofen depresses excitatory and inhibitory transmission in rat motoneurones by primarily a presynaptic mechanism in reducing the liberation of chemical transmitters from nerve endings via a phaclofen-insensitive GABAB receptor.