Effects of kappa-opioid agonist U-50488 and p38 MAPK inhibitor SB203580 on the spike activity of pyramidal neurons in the basolateral amygdala

Our study found that the KOR agonist-induced spiking activity of the BLA pyramidal neurons is mediated by the beta-arrestin pathway and can be suppressed by the application of the p38 MAPK inhibitor SB20358

Aversion-related effects of kappa-opioid agonist U-50488 on neural activity and functional connectivity between amygdala, ventral tegmental area, prefrontal cortex, hippocampus, and nucleus accumbens

This paper aims to provide an understanding of the neural activity underlying the aversion-associated effects of the KOR agonist U-5048

Effect of Clozapine and 5-NT2A-Antagonist RU-31 on electroencephalography and Motor Activity of Rats in a Model of Schizophrenia with Neonatal Destruction of the Ventral Hippocampus

Background. Schizophrenia is a socially signifi cant disease that takes a variety of forms. The form of the course determines prescribing antipsychotic drugs with a different range of clinical effects. The study of the pharmacological activity of neuroleptics involves an experimental model using animals which makes it possible to reproduce some aspects of schizophrenia.Objectives. The study is aimed at evaluating the antipsychotic activity of 5-HT2A— RU-31 antagonist and atypical neuroleptic clozapine in behavioral tests and electroencephalography (EEG).Methods. The research methodology involved a dysontogenetic model of schizophrenia, implemented via aspiration destruction of the ventral hippocampus of rats on day 7 of postnatal development. The study was carried out on white outbred male rats selected from the offspring of females, represented by a simple random sample, provided by Rappolovo animal breeding facility of the National Research Center “Kurchatov Institute”. Injection of the studied substances was initiated on day 35 of postnatal development. Motor activity was assessed on day 54 of postnatal development in the Open Field unit and included assessing vertical motor activity, measured as the number of acts of verticalization in 5 minutes, and horizontal motor activity of rats, recorded as the number of crossed squares in 5 minutes. EEG signals were recorded on day 55 of postnatal development; thereafter the spectral density was calculated in the delta- (д) (0.4–4 Hz), theta- (и) (4.8–8 Hz), alpha- (б) (8–12 Hz) and beta- (в) (12–30 Hz) frequency ranges and the effect of the “operation” and “substance” factors on spectral density was evaluated in comparison with control groups. Statistical data processing was performed using GraphPad Prism 9 (Insight Partners, USA).Results. The antipsychotic activity of 1-(2-diethylaminoethyl)-2-(4-methoxyphenyl)-imidazo[1,2-a] benzimidazole — RU-31 compound with 5-HT2A-antagonistic mechanism of action was evaluated. RU-31 compound (10 mg/kg, intraperitoneally (i.p.)) statistically signifi cantly reduced vertical and horizontal spontaneous locomotor activity in rats with psychotic disorder by 18.8% and 20.9%, while the atypical neuroleptic clozapine (2 mg/kg, i.p.) signifi cantly reduced these values by 41.15% and 27.67%, respectively. The 5-HT2A-receptor antagonist RU-31 increased EEG signal power in the delta range by 123.33% and decreased it in the alpha range by 41.86% in surgically operated animals (p < 0.05). Clozapine increased the EEG signal power in all studied frequency ranges: in delta — by 107.99%, theta — by 97.16%, alpha — by 41.86% and in beta — by 49.16% in animals with neonatal destruction of the ventral hippocampus (p < 0.05).Conclusion. The studied substances contributed to the correction of behavioural disturbances associated with hypermobility as well as electrophysiological changes induced by a surgical operation, while similar activity was not observed (or was observed to a lesser extent) in healthy animals

Investigation of the cytotoxic properties of the derivative of benzimidazole

The aim of the study - to assess the effect of the new benzimidazole derivative under laboratory cipher 203 in the test of metabolic activity of cells.Цель исследования – оценить влияние нового производного бензимидазола под лабораторным шифром 203 в тесте на метаболическую активность клеток