A comparative study of the new xylarate germanium (IV) complexe with lithium (xygerm-1), lithium chloride and valproic acid to the amphetamine-enhanced self-stimulation reactions in rats

Abstract

Aim. To estimate the effect of novel lythium bis(µ-xylarato)dihydrogermanate (IV) (Xygerm-1) on reinforcing properties of the lateral hypothalamus self-stimulation in rats compared to the reference drugs (lithium chloride and valproic acid) in rats with amphetamine-induced self-stimulation. Methods. To form a model of the brain self-stimulation, nichrome monopolar electrodes were implanted bilaterally in the lateral hypothalamic nucleus, followed by morphological control, and 7-10 days after the operation, the rats were trained to press a pedal for electrical stimulation of the brain. The effects of self-stimulation were assessed by analyzing the maximum rate of pedal pressing and the self-stimulation threshold. Study of the test compounds effects had been started when average self-stimulation threshold values varied by less than 10% for three consecutive sessions of the brain self-stimulation. Xygerm-1 (300-1800 mg/kg), valproic acid (30-300 mg/kg) and lithium chloride (25-200 mg/kg) were introduced as intraperitoneal injections to animals of the corresponding study groups (6 rats each). At the next stage of the experiment, effects of Xygerm-1, lithium chloride and valproic acid on amphetamine-induced (dose 0.5 mg/kg) brain self-stimulation reaction increase were studied at the same animal groups. Results. At the first stage of the experiment Xygerm-1 (1200 and 1800 mg/kg), lithium chloride (100 and 200 mg/kg) and valproic acid (300 mg/kg) had significantly increased self-stimulation threshold. High doses of Xygerm-1 and lithium chloride (1800 and 200 mg/kg correspondingly) had relevantly decreased the average self-stimulation rate. There was also a tendency for the average self-stimulation rate to decrease in animals administered valproic acid, though, not statistically significant. The use of Xygerm-1 and lithium chloride induced the dose-dependant self-stimulation threshold increase, decreased by the use of amphetamine sulfate. Rather high doses of Xygerm-1 and lithium chloride (1800 and 100 mg/kg correspondingly) had also blocked amphetamine-induced increase in pedal pressing rate. Studied doses of valproic acid did not altered the amphetamine-induced brain self-stimulation reaction increase. Conclusion. The novel compound bis(µ-xylarato)dihydrogermanate (IV) has a strong influence on behavior, in particular on the brain reward systems, which is similar to the action of lithium chloride and differs from the effect of valproic acid.