A. S. Bazyan

The effects of irradiation by 12C carbon ions on monoamine exchange in several rat brain structures

Rats were irradiated with carbon ions (12C) in a Nuklotron accelerator. The irradiation dose was 1 Gy, the energy of the ions was 500 MeV/nuclon, and the linear energy transmission (LET) was 10.6 keV/micron. The animals were decapitated 1 day after irradiation. We isolated the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum, where we determined the concentrations of monoamines and their metabolites. Strong changes were observed in three structures, viz., the prefrontal cortex, nucleus accumbens, and hippocampus. However, significant changes were found in the prefrontal cortex and weaker changes were seen in the nucleus accumbens, whereas changes were insignificant in the hippocampus. This reaction may be related to the fact that the animals were examined on the 2nd day after irradiation. It was shown that an increase in the interval between irradiation and examination of animals results in enhancement of the effects of radiation treatment. The experiments revealed the high sensitivity and reactivity of the prefrontal cortex, which we relate to the key role of this structure in vitally critical processes of behavior.

The effect of high-energy protons in the Bragg Peak on the behavior of rats and the exchange of monoamines in some brain structures

We studied the effects of irradiation with protons at doses of 1 and 2 Gy in the Bragg Peak with an energy of 170 MeV on learning, recall of skills, and concentration of monoamines and their metabolites in the prefrontal cortex, nucleus accumbens, hypothalamus, striatum, and hippocampus of rats. In the T-maze, we performed discriminant learning with food reinforcement. Rats were trained for 5 days; from the second to fifth days, we found a considerable level of learning as compared to the first day. After training, on the sixth day, we found a trend to a decrease in the efficacy of test performance, which achieved significant differences on the seventh day of testing. Irradiation by protons at doses of 1 and 2 Gy in the Bragg peak did not influence the elaboration and recall of the passive avoidance reflex. This treatment causes a decrease in the concentration of catecholamines in the prefrontal cortex and 3-MT, a metabolite of dopamine, in the striatum. On the basis of disturbances of neurochemical indices in the corresponding brain structures, it is possible to logically explain the observed disturbances in behavior.

Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats

Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in “open-field” tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration of monoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

Metoprine induced behavioral modifications and brain regional histamine increase in WAG/Rij and Wistar rats

The effects of metoprine, an inhibitor of histamine N-methyltransferase, on open field activity and brain regional histamine (HA) content were examined in rats with mixed, absence and audiogenic, epilepsy (WAG/Rij-AGS), rats with audiogenic epilepsy (Wistar-AGS) and in non-epileptic control rats (Wistar-nAGS). HA content was increased by metoprine (20mg/kg, i.p.) in the cortex, striatum, thalamus, hypothalamus and hippocampus of the rats from all three tested groups. However, WAG/Rij rats showed a lower rate of metoprine-induced HA accumulation in the striatum and thalamus than Wistar rats. For the open field test, the main effect of metoprine (20mg/kg, i.p.) was a general increase of locomotor activity although distinctive features, such as hyperlocomotion and exaggerated sniffing, were characteristic for the epileptic rats (WAG/Rij-AGS and Wistar-AGS, respectively). Individual rats from all the groups showed stereotyped behavior of shuttle type and head bobbing. Electroencephalographic data obtained in WAG/Rij-AGS rats confirmed that metoprine-induced behavioral activation was accompanied by suppression of spike-wave discharges, the main hallmark of absence seizures. Taken together, these results show that inhibition of the histamine catabolism may induce motor activation of particular patterns in epileptic rats and provoke stereotyped behavior.

The effects of high-energy protons and carbon ions ( 12 C) on the cognitive function and the content of monoamines and their metabolites in peripheral blood in monkeys

Model experiments using monkeys (rhesus macaque monkeys) were performed to investigate the neurobiological effects of two components of galactic cosmic radiation, namely, high-energy protons and carbon (12C) ions. It has been demonstrated that the irradiation of a monkey’s head with protons at a dose of 3 Gy did not cause any significant changes in the animal’s cognitive function and in the concentrations of monoamines and their metabolites in the peripheral blood. However, exposure to carbon ions at a dose of 1 Gy resulted in a significant cognitive function impairment and a significant decrease in serotonin metabolite concentrations in the blood in the monkeys with the excitable imbalanced type of higher nervous activity.

The dynamics of monoamine metabolism in rat brain structures in the late period after exposure to accelerated carbon ions

We studied the effect of carbon ions (12C) with an energy of 500 MeV/nucleon at a dose of 1 Gy on monoamine metabolism in the brains of rats of different ages. Neurochemical parameters that characterize the distribution of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and its metabolites were evaluated during 2 months on days 30 and 90 after the exposure to radiation. We studied the prefrontal cortex, hypothalamus, hippocampus, and striatum. The results showed changes in the activities of the NA, DA, and 5-HT systems in rats of different age groups after exposure to radiation. The most prominent differences in the exposed and control animals were observed in the prefrontal cortex and hypothalamus, which indicates the important role of these brain regions in long-term effects of exposure to radiation on the central nervous system. A comparison of animals from different age groups showed a decrease in the intensity of the temporal changes in all analyzed structures except the striatum in the exposed rats. Based on these findings, we assumed that the activation of compensatory and repairing mechanisms occurs in the late post-radiation period. At relatively low linear energy transfer of particles (10.6 keV/µm), it may lead to the partial recovery of brain functions that were impaired by radiation. At higher values of the linear energy transfer, the compensatory and recovery processes are activated to a lesser degree and functional impairment increases with time.

The distribution of monoamines and their metabolites in the brain structures of rats at later periods after exposure to 12C ions

We investigated the levels of monoamines and their metabolites in certain brain structures of rats at 30 and 90 days after exposure to carbon ions (12C) with an energy of 500 MeV/nucleon. The linear energy transfer and radiation dose were 10.6 keV/µm and 1 Gy, respectively. The concentrations of substances were measured in five structures of the brain, including the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum. On day 30 after the exposure, the most pronounced changes in the concentration of monoamines and their metabolites were observed in the nucleus accumbens; the smallest changes were found in the hippocampus and striatum. After 90 days, significant changes were still present in the nucleus accumbens. At the same time, these changes became less evident in other structures. A comparison of our results with the data of similar previous experiments (24 hours after exposure) showed that the most pronounced effect was observed soon after radiation exposure. The induced damage diminished at a later period. Based on the results of our study, we made the hypothesis that the change in the metabolism of monoamines may be compensated if the linear-energy transfer values were relatively low (10.6 keV/μm). At higher values of linear-energy transfer, compensatory and regenerative processes did not occur; the effect increased with time. An increased susceptibility of the nucleus accumbens was found at all the time points after the exposure, which may indicate an important role of this brain structure in the radiation-induced impairment of cognitive functions and emotional and motivational states.

The effects of antiorthostatic hypodynamia and overload on discriminant learning and monoamine exchange in the brain structures of mice

We studied the effects of models of imponderability (Antiorthostatic Hypodynamia, AH) and overload (AH + centrifugation) on discriminant learning in mice and the concentrations of monoamines and their metabolites in several brain structures. The experimental conditions accelerated the formation of the locomotor behavioral stereotype, which underlies discriminant food learning. This was accompanied by weaker food motivation of the experimental animals, as compared to the control animals. Presumably, this effect may be related to the so-called “sharpening of attention.” This occurs due to the suppression of the executive mechanisms of locomotor and exploratory activity, which decreases afferent generalization. Analysis of the concentrations of monoamines and their metabolites in the prefrontal cortex, hypothalamus, striatum, and cerebellum revealed considerable intensification of serotonin metabolism, in contrast to catecholamines. Behavioral results are discussed in the framework of the development of a negative emotional state related to the activity of the serotonergic system of the prefrontal cortex (“decision making” which is focused on escape from the negative state) and the realization of targeted behavior (“selection of action” as acquisition of rewards or food) by neuronal networks of the striatum and cerebellum. This response is possible with weak food motivation.