Effects of sydnocarb and D-amphetamine on the extracellular levels of amino acids in the rat caudate-putamen

The neurotoxic effects of psychostimulants at high dosages limit their clin ical applicability but the mechanism of neurotoxicity is still unsettled. W e now studied by microdialysis how acute and subchronic (four times at 2-h intervals) administrations Of D-amphetamine and sydnocarb [3-(beta -phenyli sopropyl)-N-phenylcarbamoylsydnomine], an original novel Russian psychostim ulant, affected the extracellular levels of amino acids in the caudate-puta men of halothane-anesthetized male Sprague-Dawley rats. Acute D-amphetamine administration (5.0 mg/kg, i.p.) produced a moderate accumulation of extra cellular glutamate and aspartate. Sydnocarb (23.8 mg/kg, i.p., a dose equim olar to 5.0 mg/kg D-amphetamine) also increased extracellular glutamate and alanine. Subchronic D-amphetamine administration (5.0 mg/kg x 4, i.p.) cau sed gradual fivefold increases in the glutamate and taurine levels and mode rate increases in the aspartate and alanine levels. Subchronic sydnocarb ad ministration (23.8 mg/kg X 4, i.p.) elicited a marked increase in the aspar tate level and a small increase in the level of glutamate. The alanine leve l increased temporarily after each administration of sydnocarb, while the t aurine level increased only after the last injection, We conclude that the mode of action of sydnocarb differs from that Of D-amphetamine. Sydnocarb a lso seems to be less neurotoxic than D-amphetamine, since it elicits lesser changes in the extracellular level of glutamate. (C) 2001 Elsevier Science B.V. All rights reserved.