Changes in Monoamine Levels in BALB/c and 57Bl/6N Mice in Response to Acute Stress with Different Controllability.

The severity and specificity of CNS disturbances resulting from negative psychoemotional experience are determined by not only genetically determined stress sensitivity, but also epigenetic factors; among the latter, the context of stress exposure, e.g. stress controllability is considered. We examined the effect of controllability factor on behavioral and neurochemical parameters of acute stress in the elevated plus maze test. The situations of controllable and uncontrollable stress were modeled by allowing or restricting mice in their choice for closed arms during testing in the maze. The anxiety level of inbred BALB/c and C57Bl/6N mice was assessed and the levels and monoamine turnover in the medial prefrontal cortex, hippocampus, amygdala, and hypothalamus were measured. It was found that the decrease in stress controllability suppresses explorative activity in mice; the behavioral and neurochemical differences between the two strains are not constant feature and depend on stress controllability; serotoninergic and dopaminerigic neurotransmission in the hypothalamus can be a signal to discriminate stress controllability in the brain.

Effects of amphetamine and sydnocarb on dopamine release and free radical generation in rat striatum.

Microdialysis technique was used to compare the effects of four repeated intraperitoneal administrations of two psychostimulant drugs, D-amphetamine and sydnocarb, at the equimolar doses 5 and 23.8 mg/kg, respectively, on the extracellular level of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and hydroxyl radicals (.OH) in the dorsal striatum of freely moving 3-month-old male Wistar rats 250-300 g in weight. D-amphetamine caused immediate increase of DA concentration up to 950% with quick decline towards baseline values thereafter, followed by much less increase after further injections. Sydnocarb elicited moderate elevation in DA level achieving 400% after the fourth injection. D-amphetamine induced deep decrease in DOPAC concentration, while sydnocarb caused its increase after the first and second dosing. Both drugs enhanced generation of .OH, the effect of D-amphetamine was more pronounced. D-Amphetamine induced more intensive stereotyped behavior in rats compare to sydnocarb. It is concluded that the psychostimulant action of sydnocarb is accompanied by facilitation of the central dopaminergic transmission in rat neostriatum and followed by less pronounced neurotoxic effect than that of D-amphetamine.

Effect of d-amphetamine and sydnocarb on the extracellular level of dopamine, 3,4-dihydroxyphenylacetic acid, and hydroxyl radicals generation in rat striatum.

d-AMPH and its congeners are able to produce several neurotoxic effects, including behavioral evidences of dopaminergic dysfunction, enhanced generation of reactive oxygen species, and depletion of endogenous DA. As has been shown, Sydnocarb produces a slow and gradual increase of the parameters of dopaminergic dysfunction. Present investigations report that Sydnocarb, the original Russian psychostimulant, at a dose of 23.8 mg/kg (equimolar to 5 mg/kg d-AMPH) elicited a moderate increase in the extracellular level of DA. We found that Sydnocarb increased OH generation in less degree than that by d-AMPH. Sydnocarb was also able to elicit stereotyped behavior, but to a less extent than d-AMPH. Differences between the mode of action of this drug were previously observed. In our study, the DOPAC extracellular level was significantly decreased after the fourth injection of Sydnocarb, unlike with d-AMPH treatment. Taken together, this finding probably reflects less neurotoxic potential of the novel, original psychostimulant Sydnocarb with good clinical efficaciousness in comparison to the amphetamine.