Simultaneous quantification of d- vs. l-serine, taurine, kynurenate, phosphoethanolamine and diverse amino acids in frontocortical dialysates of freely-moving rats: Differential modulation by N-methyl-d-aspartate (NMDA) and other pharmacological agents

This study describes a novel analytical method permitting simultaneous HPLC-fluorimetric quantification of multiple (15) d- and l-amino acids, kynurenate, taurine and phosphoethanolamine (a marker of membrane integrity) in microdialysates of prefrontal cortex of freely-moving rats. Levels of GABA were elevated by the transporter inhibitor, nipecotic acid, and by the transaminase inhibitor, vigabatrine. Supporting a neuronal origin, they were decreased by the GABAB autoreceptor agonist, baclofen, yet unaffected by fluoroacetate which disrupts glial metabolism. Glutamate levels were elevated by the transporter inhibitor, l-trans-PDC, and mainly neuronal since they were not decreased by fluoroacetate, yet reduced by baclofen (which recruits GABAB receptors on glutamatergic terminals) and elevated by the NMDA receptor antagonist, dizocilpine. By contrast, levels of glutamine were reduced by l-trans-PDC. Consistent with glial origin, they were unaffected by baclofen, yet reduced by fluoroacetate. Administration of d-serine selectively increased its levels over l-serine, and vice versa. d-serine modestly decreased levels of glycine, which were enhanced by administration of glycine itself and of the glycine transporter-1 inhibitor, sarcosine. Kynurenate levels were increased by its precursor, kynurenine, an effect abolished by the amino-transferase inhibitor, amino-oxyacetate. Taurine and the energy drink, Red Bull®, selectively elevated levels of taurine, which were only slightly reduced by fluoroacetate. Finally, administration of NMDA increased levels of taurine, kynenurate and phosphoethanolamine, while reducing d-serine. These actions were abolished by the competitive NMDA receptor antagonist, CPP, which was inactive alone. This broad-based dialysis system should prove instructive for exploring actions of psychotropic drugs, and for characterising animal models of CNS disorders.

► Multiple amino acids were quantified in single dialysates of rat prefrontal cortex.
► d-serine administration selectively increased its levels over those of l-serine.
► NMDA decreased levels of d-serine, and increased those of kynurenate, taurine and PEA.
► The effects of NMDA were blocked by the selective antagonist, CPP.
► Taurine and Red Bull® selectively enhanced levels of taurine vs. other amino acids.