Neuroprotective Action of Acetyl-L-Carnitine on Methamphetamine-Induced Dopamine Release

Acetyl-L-carnitine (ALC) has been shown to be neuroprotective, in a dose and time dependent manner, through a variety of processes, including: membrane stabilization, ionic homeostasis, increased expression of key proteins, decreased expression of iNOS and increased resistance to neurotoxic events. Recently, we successfully demonstrated that pre-treatment with ALC confers effective neuroprotection against MDMA-induced neurotoxicity, preventing mitochondrial oxidative damage and, most importantly, preventing the typical MDMA-induced serotonin loss. However, the mechanisms underlying these actions are still unclear. In the present work, we have exposed PC12 cells to 1 M and 100 M methamphetamine (METH) to evaluate the action of ALC (0.01, 0.05, 0.1, 0.5 and 1 mM) on dopamine (DA) function. Intra and extracellular levels of DA were measured by HPLC-EC, both after a 24 or 72 h incubation period. We show that ALC by itself increases intracellular levels of DA, which may be a direct consequence of the ALC role on tyrosine biosynthesis. We also report that ALC is capable of increasing intracellular DA levels even in the presence of high METH doses and that ALC seems to prevent METH-induced DA release, which may be regulated through ALC direct action on important membrane components.