title: 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.
abstract: 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.
authors.affiliation: Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, Paris, France. alain.gobert@fr.netgrs.com
authors.forename: Alain
authors.initials: A
authors.lastname: Gobert
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rivet
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Billiras
authors.forename: Francesca
authors.initials: F
authors.lastname: Parsons
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Millan
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D016202:N-Methylaspartate / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D018683:Excitatory Amino Acid Agents; D016202:N-Methylaspartate