[Extracellular level of neuroactive amino acids in the rat neostriatum after treatment with psychostimulants (microdialysis study)]. / Vnekletochnoe soderzhanie neiroaktivnykh aminokislot v neostriatume krys pri deistvii psikhostimuliatorov (mikrodializnoe issledovanie).

The effects of acute and subchronic (four times with a 2-h interval) intraperitoneal administration of d-amphetamine and sydnocarb in equimolar doses (5 and 23.8 mg/kg, respectively) on the intracellular level of glutamate, asparate, taurine, and alanine in neostriatum of male Sprague-Dawley rats anesthetized with halothane was studied. It was shown that repeated introduction of the psychostimulants leads to a significant increase in the content of all four neuroactive amino acids in neostriatum dyalisates. However, the effects of sydnocarb were less pronounced as compared to those of d-amphetamine, which is indicative of a lower neurotoxic potential of the former drug and confirms a significant difference in the neurochemical mechanisms of action of the two drugs studied. The massive increase in the extracellular content of taurine probably reflects hyperactivation of the glutamatergic transmission in the neostriatum and may serve as a marker of neurotoxicity.

Effects of acute toxic doses of psychostimulants on extracellular levels of excitatory amino acids and taurine in rats: comparison of d-amphetamine and sydnocarb.

We used microdialysis to study how acute toxic doses of d-amphetamine and sydnocarb [3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine], an original Russian psychostimulant, affect extracellular levels of glutamate, aspartate, and taurine in the neostriatum of halothane-anesthetized male Sprague-Dawley rats. The administration of d-amphetamine (5.0 mg/kg x 4 i.p.) caused gradual fivefold increases in the extracellular glutamate and taurine levels and moderate increases in the extracellular aspartate level. Sydnocarb administration (23.8 mg/kg x 4 i.p., a dose equimolar to 5.0 mg/kg d-amphetamine) elicited a marked increase in the extracellular aspartate level and a small increase in the extracellular level of glutamate. The extracellular taurine level increased only after the last (fourth) injection. We conclude that a massive increase in extracellular taurine reflects hyperactivation of glutamatergic neurotransmission elicited by acute toxic dose of d-amphetamine. Sydnocarb seems to be less neurotoxic than d-amphetamine, because it elicits lesser changes in the extracellular levels of glutamate and taurine.

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.