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

Abstract

The effect of baclofen, the GABAB‐agent, on the potassium‐evoked release of endogenous 5‐hydroxytryptamine (5‐HT) from slices of mouse frontal cortex has been investigated. 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. 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. 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). 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%. 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 GABAB‐receptor located presynaptically. 1987 British Pharmacological Society