Effect of Sulpiride on the Amphetamine-Induced Changes in Extracellular Dopamine,DOPAC, and Hydroxyl Radical Generation in the Rat Striatum

The neurotoxic effects of psychostimulants are mediated by several mechanisms, which together lead to neuronal damage. These mechanisms include an increase in the extracellular content of dopamine, stimulation of dopamine oxidation, accumulation of extracellular glutamate, and an increase in body temperature. In the present study, the dopamine receptor antagonist sulpiride proved able to prevent the delayed loss of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) and depressed the gradual generation of hydroxyl radicals induced in the rat striatum by D-amphetamine. However, sulpiride at a dose of 75 mg/kg × 2, coadministered with D-amphetamine (7.5 mg/kg × 4), potentiated the increase in extracellular dopamine and initially slightly enhanced D-amphetamine-induced stereotypy. The gradual increase in hydroxyl radical generation predicts the depletion of dopamine and DOPAC in the rat striatum after D-amphetamine administration, but the increase in extracellular dopamine is not a pivotal factor in the enhanced production of hydroxyl radicals.     

Semax,An ACTH(4-10) Analogue with Nootropic Properties,Activates Dopaminergic and Serotoninergic Brain Systems in Rodents

Corticotrophin (ACTH) and its analogues, particularly Semax (Met-Glu-His-Phe-Pro-Gly-Pro), demonstrate nootropic activity. Close functional and anatomical links have been established between melanocortinergic and monoaminergic brain systems. The aim of present work was to investigate the effects of Semax on neurochemical parameters of dopaminergic- and serotonergic systems in rodents. The tissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was significantly increased (+25%) 2 h after Semax administration. The extracellular striatal level of 5-HIAA gradually increased up to 180% within 1–4 h after Semax (0.15 mg/kg, ip) administration. This peptide alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites. Semax injected 20 min prior d-amphetamine dramatically enhanced the effects of the latter on the extracellular level of dopamine and on the locomotor activity of animals. Our results reveal the positive modulatory effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by d-amphetamine. Special issue dedicated to Dr. Simo S. Oja.     

Protein kinase KIN10 from <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis> as a potential regulator of primary microtubule nucleation centers in plants

The nearest plant homologues of animal protein kinase BRSK were identified using the methods of classical and structural bioinformatics. The selection was performed based on the sequence comparison, results of phylogenetic clustering, and analysis of domain architecture. Spatial structures of human BRSK1 and KIN10 from A. thaliana were compared. The relationship between KIN10 and the regulation of primary microtubule nucleation centers in A. thaliana was revealed. Obvious homology of plant KIN10 and mammalian BRSK1 evidence to suggest that this plant protein kinase is associated with the regulation of the structure and function of primary microtubule nucleation centers and is able to phosphorylate γ-tubulin from Arabidopsis (TUBG1 and TUBG2) at Ser131, affecting the γTuSC monomer structure as well as the γTuRC complex assembly. The effect of the modification on the TUBG1-GACP3 interaction was suggested.     

Lamotrigine and Carbamazepine Affect Differently the Release of D-[3H]Aspartate from Mouse Cerebral Cortex Slices: Involvement of NO

The effects of lamotrigine and carbamazepine on the release of preloaded D-[³H]aspartate and the involvement of nitric oxide were studied with mouse cerebral cortical slices in a superfusion system. Lamotrigine inhibited the veratridine-evoked release, whereas the K⁺-stimulated release was attenuated more strongly by carbamazepine than by lamotrigine. These effects were accentuated by the N-methyl-D-aspartate receptor antagonist L-2-amino-5-phosphonovalerate and the nitric oxide synthase inhibitor L-nitroarginine, but diminished by the nitric oxide donor sodium nitroprusside. The results show that in addition to the blockade of voltage-sensitive Na⁺ (and Ca²⁺) channels, NO-mediated mechanisms are probably involved in the anticonvulsant actions of carbamazepine and, in particular, those of lamotrigine.     

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.     

Bioinformatic search for plant homologs of the protein kinase Bub1—a key component of the mitotic spindle assembly checkpoint

The bioinformatic search identified 14 plant homologs of the mitotic spindle assembly checkpoint protein kinase Bub1 of animals, yeasts, and myxomycetes. It was demonstrated that the closest plant homologs of the protein kinase Bub1 were proteins with previously unknown features: XP_002274770.1 (CBI21878.1) from Vitis vinifera, EEC82122.1 from Oryza sativa Indica, EEE67244.1 from O. sativa Japonica, EEF44403.1 from Ricinus communis, and CAL57156.1 from Ostreococcus tauri. The simulation and analysis of spatial structures of the catalytic domains of the EEC82122.1, EEE67244.1, and XP_002274770.1 (CBI21878.1) proteins confirmed their conformity with the spindle assembly checkpoint protein kinases Bub1.     

Functional significance of the serotoninergic influence on neuronal activity of the somatosensory cortex in 12-day-old kittens

Monoamines, which participate in synaptic transmission as transmitters, also accomplish the modulation of neuronal activity. The role of serotonin (5-hydroxytryptamine--5-HT) was investigated in 8 to 14-day-old kittens by means of iontophoretic application onto neurones of the somatosensory cerebral cortex. The most typical response was the inhibition of neuronal activity. Another type of reaction was generated by inhibitory interneurones. After the microiontophoretic application of 5-HT, the tonic response of cortical neurones to the stimulation of the sciatic nerve changed into a phasic response. It is being suggested that the application of 5-HT to cortical neurones increases the excitability of inhibitory neurones. Hence, the serotoninergic regulation of neuronal activity in the somatosensory cortex may be operational from the 11th to the 12th day of postnatal life in cats.