Portal de Periódicos da CAPES

Kynurenic acid, by targeting α7 nicotinic acetylcholine receptors, modulates extracellular GABA levels in the rat striatum in vivo

2013; Wiley; Volume: 37; Issue: 9 Linguagem: Inglês

10.1111/ejn.12160

1460-9568

Sarah Beggiato, Tiziana Antonelli, Maria Cristina Tomasini, Sergio Tanganelli, Kjell Fuxé, Robert Schwarcz, Luca Ferraro,

Neuroendocrine regulation and behavior

Abstract Kynurenic acid ( KYNA ) is an astrocyte‐derived non‐competitive antagonist of the α7 nicotinic acetylcholine receptor (α7n AC h R ) and inhibits the NMDA receptor ( NMDAR ) competitively. The main aim of the present study was to examine the possible effects of KYNA (30 – 1000 n m ), applied locally by reverse dialysis for 2 h, on extracellular GABA levels in the rat striatum. KYNA concentration‐dependently reduced GABA levels, with 300 n m KYNA causing a maximal reduction to ~60% of baseline concentrations. The effect of KYNA (100 n m ) was prevented by co‐application of galantamine (5 μ m ), an agonist at a site of the α7n AC h R that is very similar to that targeted by KYNA . Infusion of 7‐chlorokynurenic acid (100 n m ), an NMDAR antagonist acting selectively at the glycine B site of the receptor, affected neither basal GABA levels nor the KYNA ‐induced reduction in GABA . Inhibition of endogenous KYNA formation by reverse dialysis of ( S )‐4‐(ethylsulfonyl)benzoylalanine ( ESBA ; 1 m m ) increased extracellular GABA levels, reaching a peak of 156% of baseline levels after 1 h. Co‐infusion of 100 n m KYNA abolished the effect of ESBA . Qualitatively and quantitatively similar, bi‐directional effects of KYNA on extracellular glutamate were observed in the same microdialysis samples. Taken together, the present findings suggest that fluctuations in endogenous KYNA levels, by modulating α7n AC h R function, control extracellular GABA levels in the rat striatum. This effect may be relevant for a number of physiological and pathological processes involving the basal ganglia.