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.     

The Interstrain Differences in the Effects of D-Amphetamine and Raclopride on Dorsal Striatum Dopaminergic System in KM and Wistar Rats (Microdialysis Study)

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the D2/D3 dopamine receptor antagonist raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neurotransmitter brain systems and presumably accompanied by the regulatory gene dysfunction.     

The interstrain differences in the effects of D-amphetamine and raclopride on dorsal striatum dopaminergic system in KM and Wistar rats (microdialysis study)

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the antagonist of D2 and D3 dopamine receptors raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neuromediator brain systems and presumably accompanied by the regulatory gene dysfunction.     

Development of central and peripheral serotonin-producing systems in rats in ontogenesis

The work deals with study of development of central and peripheral serotonin-producing systems in rat ontogenesis before and after formation of the blood-brain barrier. By the method of highly efficient liquid chromatography it has been shown that the serotonin level in peripheral blood before formation of the blood-brain barrier (in fetuses and neonatal rats) is sufficiently high for realization of physiological effect on target cells and organs. At the period of formation of the blood-brain barrier the serotonin level in brain sharply rises, whereas the serotonin concentration and amount in blood plasma and duodenum increase insignificantly. Completion of formation of the blood-brain barrier is accompanied by a significant increase of the serotonin content in duodenum, probably for maintenance of the high serotonin level in blood. To evaluate secretory activity, the mean rate of daily serotonin increment in the studied tissues was calculated. In brain, this parameter was maximal at the period of formation of the blood-brain barrier-from the 4th to the 16th postnatal days. This allows thinking hat brain before formation of the blood-brain barrier is the most important source of serotonin in peripheral blood.     

Heterogeneity of mu- and delta-opioid active sites in the mouse cerebral cortex. Selective increase in the affinity of a superhigh affinity delta-site during long-term administration of morphine]

The interaction of the selective mu-ligand [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) and the selective delta-ligand [D-Ser2, Leu5, Thr6]enkephalin (DSLET) with the binding sites in rat brain cortex membranes, has been studied. Analysis of the binding isotherms in the presence and absence of nonlabelled DAMGO and DSLET revealed that these ligands can interact with both superhigh affinity and high affinity binding sites that are distinct from one another. Prolonged administration of morphine and formation of physical dependence caused no appreciable changes in the parameters of either the superhigh affinity binding sites for the mu-ligands or the high affinity binding sites for mu- and delta-ligands. At the same time, the affinity of the superhigh affinity site for delta-ligands increased 3.5 times (tau 1/2 approximately equal to 17.5 h).