GABAB‐receptor mediated inhibition of potassium‐evoked release of endogenous 5‐hydroxytryptamine from mouse frontal cortex

Abstract

1 The effect of baclofen, the GABA_B-agent, on the potassium-evoked release of endogenous 5-hydroxytryptamine (5-HT) from slices of mouse frontal cortex has been investigated. 2 The release of endogenous 5-HT evoked by addition of K⁺ (35 μm) was inhibited by (±)-baclofen in a dose-dependent manner with an IC₅₀ of 0.1 μm. 3 Inhibition of K⁺-evoked release of 5-HT was produced by (±)-and (–)-baclofen but not (+)-baclofen. This action of the (–)-enantiomer was not altered by the presence of the (+)-enantiomer. 4 Addition of GABA (0.1–10 μm) also induced a dose-dependent inhibition of 5-HT release. This effect was neither enhanced by flurazepam (1 μm) nor antagonized by bicuculline (10 μm). 5 The progabide metabolite, 4-([(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)methylene]amino)butyric acid (SL75.102) (1 μm) inhibited the K⁺-evoked release of 5-HT by 61%. 6 These data suggest that baclofen is a potent inhibitor of the K⁺-evoked release of endogenous 5-HT from the cortex and further indicate that the release of 5-HT may be controlled by a GABA_B-receptor located presynaptically.