Репозиторий Университета

© 2021 Introduction: Synthetic cannabinoids are abused substances with strong psychoactive effects. Little is known about the effects on neurotransmission and the toxicity of the second-generation cannabinoid 5F-APINAC. The objective was to assess the influence of short- and long-term exposures of 5F-APINAC on metabolites associated with neurotransmission on zebrafish. Methods: Short-term (“acute”, 4 h) and long-term (“chronic”, 96 h) exposures to 5F-APINAC were performed at 0.001, 0.01, 0.1, 1.0 and 10 μM. Intervention groups were compared with a vehicle control. Each group n = 20 zebrafish eggs/larvae. Metabolites related to neurotransmission were determined. Results: In chronic exposure, larvae exposed to 10 μM 5F-APINAC presented morphological and developmental alterations. GABA had the lowest concentrations at higher exposure in acute (p < 0.01) and chronic (p < 0.001) experiments. Glutamine showed a descending trend in the acute experiment, but an ascending trend in the chronic exposure (p < 0.05). In chronic exposure, tryptophan presented an overall descending trend, but with a neat increase at 10 μM 5F-APINAC (p < 0.001). Tryptamine in acute exposure presented lower (p < 0.05) concentrations at higher doses. Dopamine and acetylcholine presented highest (p < 0.05) concentrations in the acute and chronic exposures, but with a drop at the highest doses in the chronic experiments. In chronic exposure, xanthurenic acid decreased, except for the highest dose. Picolinic acid was increased at the highest doses in the chronic experiment (p < 0.001). Conclusions: Short- and long-term exposures induced metabolomic alterations associated with the gamma-aminobutyric acid/glutamic acid, dopaminergic/adrenergic, cholinergic neurotransmitter systems, and the kynurenine pathway. Chronic exposure at 10 μM 5F-APINAC was associated with embryotoxicity confirmed by teratogenesis.

© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The study of the features of the higher mental functions of the brain in patients suffering from addiction to psychoactive substances is very important for narcology. It is necessary not only to uncover the mechanisms of addiction, a complete understanding of the neurophysiological processes that determine the nature of the development and severity of the disease, but also to solve practical problems related to the development of treatment methods and the implementation of preventive measures. Method: In the study of patients, a specially designed map was used containing information on the hereditary and demographic characteristics, on the course of the disease, as well as on the socio-cultural status of patients. To determine the functional state of cortical activity in the process of perception of unconscious signals, a special technique was used. The obtained results were subjected to dispersive analysis and the significance of differences was calculated according to Student’s t-criterion. Results: An analysis of premorbid personality traits made it possible to establish the prevalence of instability, pathological conformity, and hysteroidal features in patients. It should be noted that a large percentage of the surveyed had a hereditary burden of alcoholism, mainly in the line of the father. Curiosity, passive submission, imitation of friends were among the motives of the first drug use. All patients in the process of addiction formed the following features: increased excitability, increasing effective disorders (depression, dysphoria), aggravated by exacerbation of craving for the drug, a decline in morals and ethics (egoism, deceit, indifference to one’s fate, hedonism, loss of sense of duty), disorders of the emotional-volitional sphere (emotional instability, hypersensitivity, vulnerability). Conclusion: The analysis of the duration of latent periods and magnitude of the amplitudes of the late positive R3OO wave in patients with heroin addiction revealed clear differences between the data obtained upon presentation of an unconscious neutral and motivationally significant word. Patients who use psychoactive substances, using the method of recording induced potentials of the brain, which is a sensitive indicator of the activity of brain structures in relation to the substance used, revealed a clear diffuse activation of the cerebral cortex in response to an unconscious verbal stimulus related to the motivation prevailing in patients, in particular to “heroin”. Such activation, as well as the difficult dying out of the developed reactions to an unconscious stimulus, indicate certain neurophysiological foundations of the mechanism underlying the changes in the motivational sphere and the stability of the pathological craving for the psychoactive substance.