Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effects of Cathinones (Bath Salts) On Cultured Primary Neurons/Astroglia Cells and Neurobehavioral Functions in Mice

Tyler M. Selig
ORCID logo ,
Kevin Pierre
* ,
Rawad Daniel Arja
* ORCID logo ,
Abeer Dagra
,
Mark Gold
,
Vijaya Raghavan
,
Firas Kobeissy
,
Zhihui Yang
,
Kevin K. W. Wang
* ORCID logo
Version 1 : Received: 6 September 2022 / Approved: 8 September 2022 / Online: 8 September 2022 (09:14:34 CEST)

How to cite: Selig, T.M.; Pierre, K.; Arja, R.D.; Dagra, A.; Gold, M.; Raghavan, V.; Kobeissy, F.; Yang, Z.; Wang, K.K.W. Effects of Cathinones (Bath Salts) On Cultured Primary Neurons/Astroglia Cells and Neurobehavioral Functions in Mice. Preprints 2022, 2022090121. https://doi.org/10.20944/preprints202209.0121.v1 Selig, T.M.; Pierre, K.; Arja, R.D.; Dagra, A.; Gold, M.; Raghavan, V.; Kobeissy, F.; Yang, Z.; Wang, K.K.W. Effects of Cathinones (Bath Salts) On Cultured Primary Neurons/Astroglia Cells and Neurobehavioral Functions in Mice. Preprints 2022, 2022090121. https://doi.org/10.20944/preprints202209.0121.v1

Abstract

This study aims to examine the cytotoxicity mechanisms of synthetic cathinone (bath salts) on rat primary cultured neurons and primary astroglial cells, and to assess their neurobehavioral effects on mice. We administered methylenedioxypyrovalerone (MDPV) to both rat primary cultured neurons and primary astroglial cells to assess cell injury. We also analyzed the effects of MDPV on these cell cultures using immunocytochemistry. We utilized western blotting to assess the breakdown of αII-spectrin and glial fibrillary acidic protein (GFAP) induced by MDPV. The western blotting experiment also included calpain and caspase inhibitors (SNJ1945 and Z-D-DCB, respectively) and pro-apoptotic and pro-necrotic agents (Staurosporine and calcium ionophore A23187, respectively). Lastly, we assessed MDPV’s effects on behavioral effects using rotarod, locomotor activity, elevated plus maze, Morris water maze, forced swimming, and open field tests. MDPV caused a dose-dependent release of LDH in both cerebrocortical neuron-astroglia mixed cultures and primary astroglial cultures. MDPV also caused neurite breakages and astroglial process retraction on immunocytochemistry. Lastly, MDPV induced αII-spectrin breakdown in western blotting experiments. Co-administration of calpain and caspase inhibitors reduced the degradation of αII-spectrin and GFAP. MDPV administration also increased anxiety-like behavior and locomotor activity in the mice. Synthetic cathinones, which share structural similarities with methamphetamine, also induce significant neurotoxic effects and neurobehavioral effects on rodent models. These neurotoxic effects are likely mediated by calpain and caspase-induced apoptosis and necrosis, while astroglial death is likely only due to calpain activation. Therefore, further research may focus on pharmacological interventions targeting these pathways to mitigate the cytotoxic impact of cathinones in humans.

Keywords

Cathinones; Designer drugs; Bath salts; Neuronal injury; astroglial injury; Calpain; Caspase

Subject

Medicine and Pharmacology, Psychiatry and Mental Health

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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