Rapid and transient inhibition of mitochondrial function following methamphetamine or 3,4-methylenedioxymethamphetamine administration

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms A Proton MRS Study

“…In fact, Ernst et al (2000) reported that in methamphetamine users, the concentration of CrϩPCr was reduced significantly in the basal ganglia, but not in the frontal cortex or frontal white matter, compared to non-users. This observation is consistent with the results of previous studies, showing that the energy impairment caused by methamphetamine is localized to dopamine-rich regions (Chan et al 1994;Burrows et al 2000). Therefore, the neuronal energy impairment in the basal ganglia might participate in the pathogenesis of residual psychiatric symptoms in methamphetamine users.…”

“…However, methamphetamine-induced inhibition of mitochondria function in rats, reported by Burrows and colleagues, is rapid and transient (Burrows et al 2000). It is unclear therefore that this transient change really correlates well with long-term metabolite alterations in abstinent methamphetamine users.…”

“…In rodents, methamphetamine has been shown to decrease cytochrome oxidase activity and ATP levels in the striatum (Chan et al 1994;Burrows et al 2000). These effects of methamphetamine are selective for dopamine-rich regions, i.e., the striatum and nucleus accumbens.…”

“…In rodents and baboons, methamphetamine has been shown to be toxic to dopaminergic and serotonergic neurons (Nakayama et al 1993;Villemagne et al 1998;Kokoshka et al 1998). These neurotoxic effects include decreased concentrations of dopamine and serotonin in the brain and a reduction of dopamine and serotonin transporters, as well as loss of ATP and mitochondrial dysfunction in dopaminergic neurons (Chan et al 1994;Burrows et al 2000;Lotharius and O'Malley 2001). Human positron emission tomography (PET) studies have reported a significant reduction of dopamine transporter density in methamphetamine users Volkow et al 2001), and that the reduction observed in methamphetamine users is associated with psychomotor impairment (Volkow et al 2001).…”

Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate

“…In situations where the generation of free radicals exceeds the capacity of antioxidant defence, oxidative stress may lead to membrane degradation, cellular dysfunction and apoptosis. AMPH can enhance ROS formation through several pathways, for example, through autooxidation of dopamine with the formation of highly reactive quinines, direct inhibition of mitochondrial electron transport chain complexes and increased glutamate release (Sonsalla et al 1989, Berman and Hastings 1999, Burrows et al 2000. One reliable index of oxidative stress to proteins involves the measurement of protein carbonyl formation, resulting from the reaction of ROS with various protein side groups including lysine and arginine (Temple et al 2006).…”