Effect of chronic inhalation of toluene on behavior of rats of various age groups in multi-branched maze.

The effect of a 40-day toluene inhalation on learning of young and adult rats was examined in a multi-branched maze. Experimental rats of both age groups needed more time to pass the maze and made more errors than controls. This impairment was observed in young rats immediately after termination of toluene inhalation and in adult rats immediately and 90 days after toluene.

Effect of nadolol injected prior to CRH on stress-induced plasma corticosterone level in rat.

The proposed research is the part of our investigation of the role of catecholamines in the alterations provoked by stress. Especially, we elucidate if Nadolol injected prior to CRH ICV has some effect on plasma corticosterone level. 15 mg/kg of Nadolol (the dose sufficient to prevent CRH-induced increases in heart-rate for 2 hr), dissolved in saline was administered intraperitoneally, 30 minutes prior to CRH (The dose of interest for CRH - 1 mkg/kg - was determined earlier, as provoking the maximal increase of plasma corticosterone level after 20 minutes of its ICV injection). Whole blood was collected at 11.00 am, via indwelling jugular catheter at 0 (control) and 15 minutes after Nadolol injection, also 30 and 60 min after CRH injection. After centrifugation the plasma level of corticosterone was essayed using ELISA method. 15 minutes after Nadolol injection the level of plasma corticosterone in comparing with control wasn't changed, at subsequent time-points plasma corticosterone level was increased but significant difference was observed only after 30 minutes. Thus, according our results, 30 min after injection, the dose of Nadolol, sufficient to prevent CRH-induced increase in heart rate, doesn't preclude the CRH-induced increase of plasma corticosterone - one of key signs of the stress-axis activation. The results were discussed.

Stress-system: corticotropin-releasing hormone and catecholamines (review).

The brain's stress-handling system--the limbic-hypothalamic-pituitary-adrenal axis--is one of the most thoroughly studied circuitry of the central nervous system. As a result of stress-axis activation different behavioral and physical changes develop; these changes allow the organism to adapt. For this purpose stress-system closely "works" with other elements of central nervous system, which are involved in the regulation of emotion and structures, also with axes, responsible for reproduction, growth and immunity. Dysfunction of stress-system--it's hyper- or hypoactivity--is characteristic peculiarity of many pathological states and disorders. Various molecules (corticotropin-releasing hormone, vasopressin, glucocorticoids, mineralocorticoids, ACTH, its precursor proopiomelanocortin etc.) are engaged in the regulation of stress-axis. Among these molecules corticotropin-releasing hormone is supposed to have a key role in regulating the response to stress. Besides these molecules, the end-products of the stress-axis activation: catecholamines, different hormones and cytokines - control the activity of multiple levels of this axis. According some views catecholamines play one of the essential roles in the alterations provoked by stress-axis activation. In this review we cite some classical (Crousseau et al.) and modern data concerning corticotropin-releasing hormone and catecholamine activities during stress.

Pyramidal cell loss in hippocampus of young rats exposed to toluene.

In the present study the influences of toluene intoxication on quantity of the pyramidal and granular cells in hippocampus was analysed in young and adult rats. An inhalation route of intoxication was used in our experiments - animal inhaled toluene until attaining a sidewise laying position. This procedure was performed in the closed glass container, in which air was beforehand saturated with the toluene vapors. Experiments was carried out on two age groups (n=20): one and two months age rats. Inhalation period was 40 days, Each age group consisted of ten animals and was divided into the two subgroups: I - control animals (n=5), II - experimental animals (n=5). Assessment of the neurons' quantity in different structures was made according to the fractional approach method proposed by M. West. The results obtained showed that number of the pyramidal neurons decreases by 26% (I - 1067+/-83,8; II - 786+/-7; p<0,05) against the control in CA-3 field of the Subgroup II of the younger animals only. In the dentate fascia number of the granular cells does not change in either age group. Loss of pyramidal cells in the CA-3 field will induce deterioration of the hippocampal neural circuits and destroy of memory and learning processes in the rats.

Influence of toluene intoxication on the number of mitral and granular neurons in olfactory bulbs of rats.

In the last years, implementation of the volatile solvents in order to get a narcotic high, used via inhalation (sniffing), increased significantly, especially in the youth. Substances containing these agents induce hallucinations and euphoric state. In the present study the influences of toluene intoxication on quantity of the mitral and granular cells in olfactory bulbs was analyzed in young and adult rats. An inhalation route of intoxication was used in our experiments - animal inhaled toluene until attaining a sidewise laying position. This procedure was performed in the closed glass container, in which air was beforehand saturated with the toluene vapours. Experiments was carried out on two age groups (n=20 animals): one - and two months age rats. Inhalation period was 40 days. Each age group consisted of ten animals and was divided into the two subgroups: I - control animals (n=5), II - experimental animals (n=5). Assessment of the neurons' quantity in different structures was made according to the fractional approach method proposed by M. West (1999). The results obtained showed that number of mitral neurons in the olfactory bulb of the Subgroup II of the rats, sniffing since the age of one and two months, significantly decreased by 43% (p<0,05) and by 28% (p<0,01), respectively. Meanwhile, the granular cells remained unaltered in experimental animals of both age groups. Decrease of the projection mitral neurons, in its turn, results in disruption of the projections to olfactory cortex and hampers proper functioning of the olfactory analyzer.

[Effect of toluene on stability of chromatin of white rat hippocampus and olfactory bulb in vivo. Microcalorimetric study].

The denaturation heat parameters of hippocampus and olfactory bulb nodulus tissues were determined. The total denaturation heat calculated from the areas of endotherms I-IX onto which the dependence deltaH = f(T) is factorized equals to 13.03 +/- 1.3 J/g for bulb nodules and 9.91 J/g for the hippocampus. It was shown that chromatin in the composition of tissues had two stages of denaturation with the following parameters: for bulb nodules: Td(VIII) = 99.4 degrees C, Qd(VIII) = 62.3 +/- 0.8 J/g DNA, Td = (IX) = 106 degrees C, Qd = 28.8 ; 0.4 J/g DNA; and for hippocampus: Td(VIII) = 95 degrees C; Qd(VIII) = 62.0 +/- 9 J/g. Td(IX) - 107 degrees C; Qd(IX) = 29.0 +/- 4.5 J/g DNA. It was established that, along with denaturation of cytoplasmatic structures, nonhistone, nuclear proteins and damage to the nuclear matrix, toluene caused the redistribution of heat between endotherms IX, VIII, VIII(I) connected with the infolding of chromatin loops and 30-nm fibers. It is supposed that toluene causes the damage to the genetic material due to not only its oxidative influence on chromatin DNA but also the disturbance of nuclear matrix structural organization and partial denaturation of nuclear proteins of non-histone origin.