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 clinical applicability but the mechanism of neurotoxicity is still unsettled. We now studied by microdialysis how acute and subchronic (four times at 2-h intervals) administrations of D-amphetamine and sydnocarb [3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine], an original novel Russian psychostimulant, affected the extracellular levels of amino acids in the caudate-putamen of halothane-anesthetized male Sprague-Dawley rats. Acute D-amphetamine administration (5.0 mg/kg, i.p.) produced a moderate accumulation of extracellular glutamate and aspartate. Sydnocarb (23.8 mg/kg, i.p., a dose equimolar 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.) caused gradual fivefold increases in the glutamate and taurine levels and moderate increases in the aspartate and alanine levels. Subchronic sydnocarb administration (23.8 mg/kg x 4, i.p.) elicited a marked increase in the aspartate level and a small increase in the level of glutamate. The alanine level increased temporarily after each administration of sydnocarb, while the taurine level increased only after the last injection. We conclude that the mode of action of sydnocarb differs from that of D-amphetamine. Sydnocarb also seems to be less neurotoxic than D-amphetamine, since it elicits lesser changes in the extracellular level of glutamate.