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E V Gurevich

Publications and source records attributed to E V Gurevich.

24 records · Page 2Linked to original sources

Effects of bulbectomy and subsequent antidepressant treatment on brain 5-HT2 and 5-HT1A receptors in mice.

The effects of bilateral olfactory bulbectomy on serotonergic 5-HT2 and 5-HT1A receptor binding were studied in the frontal cortex (FC), limbic structures (LS), including the hippocampus, amygdala, olfactory tubercule, and piriform cortex, and hypothalamus (HTH) in mice. Bulbectomy resulted in the increase of Bmax for [3H]spiperone binding with 5-HT2 receptors in FC in C57Bl/6j. The receptors in LS and HTH remained unchanged. Subchronic treatment of the bulbectomized mice with antidepressant trazodone (20 mg/kg/day, IP, 14 days) induced downregulation of 5-HT2 receptors in FC and LS. The other two antidepressants used, amitriptyline (20 mg/kg/day, IP, 14 days) and imipramine (10 mg/kg/day, IP, 14 days), did not alter these receptors. [3H]8-OH-DPAT binding with 5-HT1A receptors was not altered by bulbectomy in any brain area in C57Bl/6j mice. Amitriptyline and trazodone decreased Bmax for these receptors in FC in the bulbectomized mice while imipramine was ineffective. Amitriptyline and imipramine significantly increased Bmax and decreased Kd in HTH, and trazodone displayed the same tendency. Bulbectomy did not alter 5-HT2 receptors in DBA/2j mice. Amitriptyline increased Kd in the all brain areas without changing Bmax in the bulbectomized DBA/2j mice. Trazodone significantly decreased Bmax in FC and increased Kd in FC and LS. Imipramine decreased Bmax while increasing Kd in LS. The possible involvement of the serotonin receptor subtypes in the bulbectomy-induced behavioral deficits and in the restorative action of the antidepressants is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Dissociation of multiple behavioral effects between olfactory bulbectomized C57Bl/6J and DBA/2J mice.

The behavioral effects of bulbectomy and subsequent antidepressant treatment in two mice strains were compared on measures of open field behavior and passive and active avoidance 2 and 4 weeks after surgery. After bulbectomy, both strains displayed elevated locomotion in open field, corrected by antidepressants. Enhanced rearing was decreased by antidepressants in C57Bl/6J, but not in DBA/2J mice. Passive avoidance, being intact 2 weeks after surgery in both strains, was strongly impaired 4 weeks after bulbectomy in C57Bl/6J mice, with antidepressants restoring the performance. Active avoidance acquisition and retention were also dramatically disturbed in C57Bl/6J mice 2 and 4 weeks after surgery, and antidepressants had recuperative effect. In contrast, bulbectomized DBA/2J mice didn't show any significant passive or active avoidance deficits, and antidepressant treatment seemed to have no effect on their learning ability. The observed strain differences suggest that bulbectomy may produce quite diverse neurophysiological and neurochemical alterations in two strains.

Amitriptyline↗

[The role of the brain monoaminergic systems in the effects of tuftsin and its analog on animal emotional behavior].

The effects of tuftsin and its analogue TP-1 (300 micrograms/kg) on the animal adaptive behaviour in emotionally different situations, the level of biogenic amines and their metabolites 10, 30 min., 2 and 6 hrs after injection of these substances were studies. The TP-1 induced an increase in the memory traces stability better than tuftsin in emotionally negative situation. A single injection of the peptides induced changes in NA, DA and their metabolites contents for 30 min. to 2 hrs. In contrast to tuftsin, the TP-1 activated the metabolism of 5-HT in the hypothalamus and caudal brainstem without changing the NA turnover. The data obtained suggests that a stronger psychotropic activity of the TP-1 seems to be caused by its obvious effect on biogenic amines and their metabolites level in the brain.

Adaptation, Physiological↗

Limbic circuits and monoamine receptors: dissecting the effects of antipsychotics from disease processes.

There is considerable evidence for the involvement of brain dopaminergic and serotonergic systems in schizophrenia pathology. However, post-mortem studies have been limited by difficulties in separating the effects of chronic exposure to antipsychotics from that of the disease process. Our recent studies directly explored this by comparing groups that were free from antipsychotic treatment for up to a year prior to death and that were maintained on antipsychotics. We have used this approach to identify that there are prominent effects of both disease and of antipsychotic treatment. There appears to be a high association for schizophrenics between elevations of D3 receptors in target regions of the mesolimbic dopamine (DA) system and elevated numbers of 5-HT(1A) receptors in prefrontal cortex (PFc). Antipsychotic treatment was correlated with a reduction of D3 receptors in the ventral striatum and its output structures. It also led to a reduction in the number of 5-HT2 receptors in some regions of the PFc without modifying the concentration of 5-HT(1A) receptors. The limbic loop interconnecting the PFc and ventral striatum may be the site of antipsychotic regulation of certain symptoms in schizophrenia, particularly anhedonia and depression. The positive symptoms of schizophrenia are more likely to be associated with disturbances in the temporal lobe. However, dopaminergic systems in the temporal lobe have historically been thought to be underdeveloped compared to that in the basal ganglia and unlikely to be the target of antipsychotics. Our studies of the expression of the DA D2 receptor in the temporal lobe has shown a complex organization in the perirhinal and temporal cortices that is disrupted in schizophrenia. The disturbances, which might be of neurodevelopmental origin and are unrelated to antipsychotic treatment, include altered laminar distribution of the D2 receptor and modified modular organization of D2 receptors in the superior temporal gyrus. We hypothesize that modified expression of D2 receptors in these regions play a key role in the genesis of hallucinations. Treatment with antipsychotics leading to D2 receptor blockade in temporal cortex may reduce the presence of positive symptoms.

Antipsychotic Agents↗

[The behavioral and biochemical sequelae of the removal of the olfactory bulbs in C57Bl/6j mice].

Ablation of the olfactory bulbs in mice C57Bl/6j was accompanied by motor and orienting-exploratory activity augmentation in the "open field" test and deterioration of the learning ability to active and passive avoidance. The most expressed behavioural changes developed in four weeks after the surgery. Chronic administration of antidepressants (amitriptyline, 20 mg/kg; trazodone, 20 mg/kg; imipramine, 10 mg/kg; intraperitoneally) normalized behaviour of bulbectomized animals, trazodone being the most effective. In the biochemical studies the brainstem serotonin level was found to be decreased and the density of 5HT2-receptors in the cerebral cortex increased in bulbectomized mice. Only trazodone was able to correct the biochemical indices. The state of the bulbectomized mice is supposed to serve a model of a depression with hypo-function of serotonergic system of the brain.

Amitriptyline↗

[Effect of 8-Br-cAMP on the formation of conditioned reflex behavior in the white rat].

The influence of cAMP analogue 8-Br-cAMP on conditioning was studied in white rats. Two models of learning were used with different kinds of reinforcement, i. e. conditioned active avoidance and instrumental alimentary reactions in a complex maze. Intraventricular 8-Br-cAMP injection 4 or 24 hours before the beginning of learning improved the process of defensive as well as alimentary conditioning. Characteristics of formation of complex behaviour of experimental rats in a maze showed that under the influence of 8-Br-cAMP, not only conditioning was accelerated, but the process of optimal decision making itself was changed. The data obtained permit to suppose that 8-Br-cAMP first of all affects initially poorly learning rats.

8-Bromo Cyclic Adenosine Monophosphate↗