Specifics of Experimental Modeling 8-OH-DPAT-Induced Perseverative Behavior in Mice.

The effect of 5-HT1A receptor agonist 8-OH-DPAT (intraperitoneal injection in doses of 1, 2, and 4 mg/kg) on spontaneous alternation behavior of mice in Y-maze was studied without and with habituation procedure and food reward. In the first case, 8-OH-DPAT administration led to a decrease in spontaneous alternation and locomotor activity in mice. At the same time, 8-OH-DPAT treatment after habituation and food deprivation increased repeated choices of goal arms without affecting locomotor activity, which was consistent with perseverative behavior. 8-OH-DPAT-induced decrease in spontaneous alternation behavior in Y-maze in mice with habituation and food reward is the most suitable procedure for experimental modeling of the perseverative behavior and studying the anticompulsive activity of new substances.

The Behavioral and Neurochemical Aspects of the Interaction between Antidepressants and Unpredictable Chronic Mild Stress.

The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corresponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine - but not of amitriptyline - after a single injection coincided with an increase in the 5-HT turnover in the hippocampus. Chronic administration of the antidepressants increased the hypothalamic levels of NA. Thus, the antidepressant- like effect of amitriptyline and fluoxetine may result from an enhancement of the stress-dependent adaptive mechanisms depleted by chronic stress.

The Levels of Monoamines and Their Metabolites in the Brain Structures of Rats Subjected to Two- and Three-Month-Long Social Isolation.

The levels of monoamines and their metabolites in the brain structures of adult Wistar rats subjected to post-weaning social isolation for 2 and 3 months were analyzed by HPLC with electrochemical detection. We have previously shown that these rats consistently demonstrate increased aggressiveness and, as a rule, impairment of short-term habituation. Two-monthlong social isolation was accompanied by a reduction in serotonin content and its increased turnover judging from the 5-HIAA/5-HT ratio in the hippocampus; three-month-long isolation was associated with increased levels of serotonin and reduction in its turnover in the amygdala. At this term, the level of dopamine metabolite 3-methoxytyramine tended to increase in the amygdala. In the frontal cortex, a tendency to a decrease in 5-HT level was found. These findings suggest that more prolonged post-weaning social isolation is accompanied by reorganization of neural networks in the brain cortex, which can serve as the pathophysiological basis for psychoemotional disorders.

[NEUROCHEMICAL STUDY OF TROPOXIN EFFECTS ON THE CONTENT OF MONOAMINES AND ITS METABOLITES IN WISTAR RAT BRAIN STRUCTURES].

The influence of perspective anti-migraine drug tropoxin on the content of monoamines and related metabolites in Wistar rat brain structures, including frontal cortex (FC), hypothalamus, nucleus accumbens (NA), striatum, and hippocampus, has been studied using HPLC/ED technique. Tropoxin (10 mg/kg) induced a 30% decrease (p < 0.05) in dopamine (DA) level in FC as well as norepinephrine content in NA, while the concentrations of DA metabolites DOPAC and HVA in the hypothalamus were found to increase. The injection of tropoxin in a dose of 20 mg/kg led to an increase in HVA level in hypothalamus as well as seroto- nin metabolite 5-HIAA content in NA. The obtained data provide evidence that tropoxin predominantly influenced the activity of dopaminergic system while the drug effects on the parameters of serotoninergic link seem to be rather mild.

[STUDYING ANXIOLYTIC AND ANTIDEPRESSANT PROPERTIES OF 2,2,6,6-TETRAMETHYLPIPERIDONE DERIVATIVE.]

Neuropharmacological properties of LK-998 (3,4,5-trimethoxy-N'-(2,2,6,6-tetramethylpiperidin-4-yliden)benzohydrazide), a 2,2,6,6-tetramethylpiperidone de- rivative have been studied. LK-998 exhibited anxiolytic activity in doses of 10 and 20 mg/kg, significantly increasing the duration of animal staying of in open arms of the elevated plus maze as well as the number of arm entries. The efficiency of drug tested in a dose of 10 mg/kg was comparable with that of afobazole in a dose of 5 mg/kg. In marble burying test, it was also found that animals treated with LK-998 at 10 mg/kg buried a close number of balls to that as rodents treated with afobazole at 5 mg/kg. At the same time, LK-998 in doses 10 and 20 mg/kg did not produce any antidepressant action in the learned helplessness test. Thus, LK-998 in a dose of 10 mg/kg has anxiolytic and anticompulsive effects comparable to those of afobazole at a dose of 5 mg/kg. The study of potenti- al side effects of LK- 998 in a dose of 200 mg/kg (i.e., 20 times the therapeutic dose of 10 mg/kg) showed that the drug tested caused neither side effects nor symptoms of neurological deficiency within 24 hours and on longer terms (4, 10 and 14 days after administration).