A Method for Chronic Registration of Brain Cortical Electrical Activity in Rats

Sysoev, Yu. I.; Prikhodko, Veronika A.; Idiyatullin, R. D.; Chernyakov, R. T.; Карев, В. Е.; Оковитый, С. В.

doi:10.1134/s0022093022010252

Cited by 4 publications

(1 citation statement)

References 18 publications

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“…While the full spectrum of U-50488's effects on brain function and neural circuits remains incompletely understood, insights that bridge this gap can be gleaned from local field potential analyses. The study of LFP (as well as ECoG and EEG) offers a direct window into the network-level oscillatory activity of neuronal populations and yields valuable information about inter-regional interactions (Bressler 2021;Sysoev et al 2022a).…”

Section: Introductionmentioning

confidence: 99%

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

Kalitin,

Spasov,

Mukha

2023

RRP

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Introduction: Among the various receptor systems in the brain, the opioid receptors have been the subject of extensive research due to their integral role in pain modulation, reward processing, and emotional regulation. The kappa-opioid receptor (KOR) system, in particular, stands apart due to its unique contribution to stress response, aversive behaviors, and dysphoric states. This paper aims to provide an understanding of the neural activity underlying the aversion-associated effects of the KOR agonist U-50488. Materials and Methods: Rats underwent stereotaxic surgery to implant electrodes into the amygdala, ventral tegmental area, prefrontal cortex, hippocampus, and nucleus accumbens. The rats were subjected to conditioned place preference test to measure aversion to U-50488. After that, local field potential (LFP) recordings were made. LFP data were processed and analyzed using spectral and coherence analysis methods. A stepwise multiple linear regression was employed to identify the LFP features most significantly correlated with aversion to U-50488.Results: The administration of U-50488 resulted in significant changes in LFP signals across multiple brain regions. These changes were particularly notable in the theta, gamma, and delta bands of brain waves (p<0.05). Theta and gamma activities were especially sensitive to the effects of U-50488. Connectivity calculations revealed shifts in coherence between brain regions, particularly highlighting the amygdala's involvement. While changes were also observed in the ventral tegmental area, prefrontal cortex, hippocampus, and nucleus accumbens (p<0.05), they contributed less to aversion. Using the stepwise multiple linear regression method, we established a final model with the 3 most significant variables: (1) coherence between the amygdala and medial prefrontal cortex, (2) coherence between the amygdala and hippocampus, and (3) theta power in the amygdala. Conclusion: Overall, the data provided insights into how electrical neural activity mediates aversion in response to KOR activation. The results showed that the severity of aversion can be reasonably predicted (r = 0.72±0.02, p = 0.0099) using LFP band power and functional connectivity data. We concluded that the amygdala is a brain region that contributes the most to the KOR agonist-induced aversion.

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Section: Introductionmentioning

confidence: 99%

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

Kalitin,

Spasov,

Mukha

2023

RRP

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Pharmacoencephalographic Assessment of Antiphyschotic Agents’ Effect Dose-Dependency in Rats

Sysoev,

Shits,

Puchik

et al. 2023

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova

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Pharmacoencephalography (pharmaco-EEG) is a prominent instrument for the pharmacological screening new psychoactive molecules. This experimental approach has not remained a vestige of neurobiological studies, and can be used successfully to complete today’s research objectives. The development and rise to universal use of machine learning techniques opens up novel prospects for the use of pharmaco-EEG data to solve the problems of classification and prognosis. We have previously shown that naïve Bayes classifier (NBC) combined with the principal component analysis (PCA) can be used to differentiate between antipsychotic and sedative drug effects as well as to distinguish among the antipsychotics’ effects. In the present study, we evaluated the possibility to employ this method to assess the dose-dependency of antipsychotic effects. The experiments were carried out in white outbred male rats with chronically implanted electrocorticographic electrodes. As the agents of interest, we chose two drugs with antipsychotic activity, chlorpromazine and promethazine, in three doses each (0.1, 1, 10 mg/kg and 0.5, 5 and 20 mg/kg, respectively). The training set, used as a reference to determine the pharmacological effects of the agents of interest, included the D2-dopamine receptor blocker haloperidol, M-cholinergic receptor blocker tropicamide, H1-histamine receptor blocker chloropyramine, the sedative dexmedetomidine, and the anxiolytic phenazepam. We have shown that the lowest chlorpromazine dose (0.1 mg/kg) can be characterized as antipsychotic with a marked histaminolytic effect, while the highest one (10 mg/kg) exhibits predominantly antipsychotic activity with a cataleptogenic effect. All the doses demonstrated anticholinergic activity, which increased with the dose. For promethazine, we observed a clear dose-dependent transition from antipsychotic action to cataleptogenic, alongside a notable antimuscarinic effect of all doses. None of promethazine doses showed any resemblance to chloropyramine, which probably indicates its anti-dopaminergic and antimuscarinic effects being able to mask its H1-antihistamine effect in the used dose range. In summary, our results demonstrate that NBC coupled with PCA can be used to determine the dose-dependency of antipsychotic agents’ effects based on their impact on electrocorticogram parameters. Further development of this method as well as expansion of psychotropic agent electropharmacogram library would allow for more precise prognosis of pharmacological activity of the agents of interest.

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Pharmacological screening of a new valproic acid derivative using the pharmacoencephalography method in rats

Sysoev,

Shits,

Puchik

et al. 2024

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. The naïve Bayes classifier combined with principal component analysis allows to distinguish the effects of antipsychotic agents effectively as well as evaluate their dose-dependency based on their impact on electroencephalogram parameters in rats. Further development of this method requires its validation as an instrument for the screening of new understudied molecules. Valproic acid derivatives appear to be a promising neuropharmacological group as they exhibit not only antiepileptic activity but also mood-stabilizing, antimigraine, neuroprotective and analgesic effects.Aim. This work was carried out to perform the pharmacological screening of a valproic acid aminoester (AVA) that exhibits antidote properties in case of poisoning with anticholinesterase agents.Materials and methods. The experiments were conducted in white outbred rats with chronically implanted electrocorticographic electrodes. AVA was administered at doses of 0,5, 5 and 30 mg/kg. The training set, used as a reference to determine the pharmacological effects of each dose of the investigated substance, included matrixes of effects of 7 drugs: the antiepileptic agent sodium valproate, the D2-dopamine receptor blocker haloperidol, the M-cholinergic receptor blocker tropicamide, the H1-histamine receptor blocker chloropyramine, the acetylcholinesterase inhibitor galantamine, the sedative dexmedetomidine, and the anxiolytic phenazepam.Results and discussion. AVA at the dose of 0,5 mg/kg showed effects similar to those of sodium valproate, while a tenfold dose increase led to the predominance of an atropine-like effect. When administered at the dose of 30 mg/kg, the compound exhibited dexmedetomidine-like action. The central M-anticholinergic effect of AVA was confirmed by an arecoline test in mice, in which the substance at a dose of 88 mg/kg completely abolished the onset of tremor. Dexmedetomidine-like action was cancelled by the administration of atipamezole in equimolar quantities, which may indicate the potential сapability of AVA to activate α2-adrenergic receptors at a high dose. The results of molecular docking suggest that this effect is related specifically to the original aminoester molecule and not to its presumable active metabolites.Сonclusion. The obtained results confirm the effectiveness of the naïve Bayes classifier as an instrument for the prediction of the pharmacological activity of compounds based on their impact on electroencephalogram parameters in rats. Identification of new pharmacological effects of understudied compounds may widen the potential range of their clinical application as well as reveal probable adverse effects.

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A Method for Chronic Registration of Brain Cortical Electrical Activity in Rats

Cited by 4 publications

References 18 publications

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

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

Pharmacoencephalographic Assessment of Antiphyschotic Agents’ Effect Dose-Dependency in Rats

Pharmacological screening of a new valproic acid derivative using the pharmacoencephalography method in rats

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