On the necessity of translational cognitive-neurotoxicological research in methamphetamine abuse and addiction

Abstract

high-risk behaviors, treatment non-adherence, and repeated relapses. This ultimately contributes to maintaining continuous drug-seeking behaviors (Cadet and Bisagno 2015), and thus indirectly enhances all of the toxicological effects of METH abuse. METH is often consumed for its effects which, among others, include increased energy levels and decreases in fatigue, increased psychomotor activity and alertness, anorectic effects, increases in sex drive, and euphoria. Yet, irritability, agitation, risky sexual behaviors, (motor) stereotypies, psychosis, seizures, hyperthermia and other systemic effects are also common acute (side) effects of METH consumption (Panenka et al. 2013;Cadet and Bisagno 2015;Chomchai and Chomchai 2015). Those effects are mainly attributed to increases in both central and peripheral monoaminergic signaling, with strong effects in the noradrenergic (NA) and dopaminergic (DA) systems (5-HT) (Schep et al. 2010;Carvalho et al. 2012). Repeated consumption causes striking and long-lasting dysfunctions in monoaminergic signaling which are characterized by decreases in the levels of monoamines and their metabolites, monoamine transporter-binding sites, lower expression and/or activity of enzymes involved in the synthesis and metabolism of brain monoamine neurotransmitters, and neurodegeneration (especially of dopaminergic nerve terminals) (Carvalho et al. 2012;Halpin et al. 2014). Other indirect acute neuronal effects of METH include the release of glutamate in cortical and subcortical regions as well as glia activation (Rocher and Gardier 2001;Carvalho et al. 2012).While these effects are well known, they have mostly been regarded to affect the consuming individual. In this regard, recent findings in animals by Fujaková-Lipski et al. (2017) have shown transgenerational effects of METH exposure by looking at how neurotoxic effects of METH administered in utero alter various neurotransmitter Keywords Addiction · Methamphetamine · Neurotoxicity · Translational Humans have been consuming stimulants like amphetamine in the form of cathinone (khat) for thousands of years, but since world war two, synthetic amphetamines, especially methamphetamine (METH), have hit many societies in a worldwide surge (Carvalho et al. 2012). Due to its highly addicting properties and the comparatively low cost, the abuse of this psychostimulant has rapidly increased in the last decades and years (Chomchai and Chomchai 2015) so that METH has become one of the most abused substances worldwide (Bernheim et al. 2016). Continued METH consumption does not only have devastating effects on the health and well-being of the addicted individuals, but also affects whole communities and put a considerable strain on healthcare systems (Panenka et al. 2013;Chomchai and Chomchai 2015). In addition, while all forms of METH toxicity are undoubtedly harmful to the affected individual, we think that it is worth to direct special attention to the neurotoxic effects and as the associated neurocognitive impairments (especially deficits in execu...

Assessing the Effect of Diazepam on Methamphetamine-Induced Seeking Behavior in Rats

“…There are evidence indicating that dopaminergic stimulation in the mesocorticolimbic system, especially in the nucleus accumbens, is responsible for methamphetamine and cocaine rewards phenomena (5). Methamphetamineinduced damage not only degenerates dopaminergic (DA) nerve terminals, but also reduces dopamine transporter (DAT) activity, tyrosine hydroxylase activity, and vesicular monoamine transporter-2 (VMAT) protein levels (6,7). Decreased concentrations of DA and DA metabolites have been shown in several brain regions of rodents or nonhuman primates following repeated administration of Copyright © 2021, Author(s).…”