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Role of nitric oxide in psychostimulant-induced neurotoxicity

1 Laboratory of physiology of reinforcement, P.K. Anokhin Institute of Normal Physiology, Moscow, Russia
2 Department of Pharmacology and Toxicology, University of Innsbruck, Austria

Special Issues: Special Issue on Neuronal Nitric Oxide

In recent decades, consumption of psychostimulants has been significantly increased all over the world, while exact mechanisms of neurochemical effects of psychomotor stimulants remained unclear. It is assumed that the neuronal messenger nitric oxide (NO) may be involved in mechanisms of neurotoxicity evoked by psychomotor stimulants. However, possible participation of NO in various pathological states is supported mainly by indirect evidence because of its short half- life in tissues. Aim of this review is to describe the involvement of NO and the contribution of lipid peroxidation (LPO) and acetylcholine (ACH) release in neurotoxic effects of psychostimulant drugs. NO was directly determined in brain structures by electron paramagnetic resonance (EPR). Both NO generation and LPO products as well as release of ACH were increased in brain structures following four injections of amphetamine (AMPH). Pretreatment of rats with the non-selective inhibitor of NO- synthase (NOS) N-nitro-L-arginine or the neuronal NOS inhibitor 7-nitroindazole significantly reduced increase of NO generation as well as the rise of ACH release induced by AMPH. Both NOS inhibitors injected prior to AMPH had no effect on enhanced levels of LPO products. Administration of the noncompetitive NMDA receptor antagonist dizocilpine abolished increase of both NO content and concentration of LPO products induced by of the psychostimulant drug. Dizocilpine also eliminated the influence of AMPH on the ACH release. Moreover, the neurochemical and neurotoxic effects of the psychostimulant drug sydnocarb were compared with those of AMPH. Single injection of AMPH showed a more pronounced increase in NO and TBARS levels than after an equimolar concentration of sydnocarb. The findings demonstrate the crucial role of NO in the development of neurotoxicity elicited by psychostimulants and underline the key role of NOS in AMPH-induced neurotoxicity.
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Keywords nitric oxide (NO); psychostimulant drugs; neurotoxicity; brain; striatum; electron paramagnetic resonance; amphetamine; Sydnocarb; NO synthase inhibitors; lipid peroxidation; antagonist NMDA glutamate receptor

Citation: Valentina Bashkatova, Athineos Philippu. Role of nitric oxide in psychostimulant-induced neurotoxicity. AIMS Neuroscience, 2019, 6(3): 191-203. doi: 10.3934/Neuroscience.2019.3.191


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