Baclofen (β-p-chlorophenyl-γ-aminobutyric acid) enhances [3H]γ-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro

Abstract

The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic G AB A mechanisms in vitro. (±)-Baclofen (300 μM-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with ³H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen: neither the (—)-isomer nor another neuronal depressant DL-α-∞-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither β–phenethylamine nor dopamine evoked release of ³H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [³H]β-alanine or [³H]diaminobutyric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (β-alanine and (±)-cis-1,3-amino-cyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [³H]GABA release. Baclofen also inhibited uptake of [³H]GABA into pallidal slices with an IC50 value of 6 × 10⁻⁴ M. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (—)-isomer. The potential of the (+)-isomer as an antipsychotic agent while (—)-baclofen remains the effective antispastic drug free from unwanted side-effects, is discussed.