Methamphetamine (METH) is a highly addictive psychostimulant drug that injures monoaminergic neurons and results in behavioral impairments in humans and animals. Acetyl-L-carnitine (ALC) is an endogenous quaternary ammonium compound that forms part of the intracellular carnitine system, plays a vital role in the mitochondrial oxidation of fatty acids, and shows a protective and regenerative action profile on the nervous tissue after toxic or traumatic injuries. The purpose of this study is to examine whether ALC can reverse the METH-induced neurotoxicity and behavioral deficits. Male ICR mice were treated with METH (4%D75 mg/kg s.c., 2 hour apart) or saline. Behavioral tests including novel location recognition test (NLRT), novel object recognition test (NORT), and social interaction were examined 7 days later to validate the behavioral effects of METH. Subsequently, ALC (30 or 100 mg/kg, i.p.) was administered once daily for seven consecutive days. ALC significantly restored the cognition deficits, social withdrawal, and lower levels of tyrosine hydroxylase in the striatum after METH treatment. In addition, METH reduced glial cell linederived neurotrophic factor (GDNF) expression in the hippocampus and this effect was reversed by ALC. These findings suggest that ALC might exert its neurorestorative effects, at least in part, through GDNF and have therapeutic potential for the treatment of behavioral abnormality in METH abusers.
Date:
2011-08
Relation:
Journal of Neurochemistry. 2011 Aug;118(Suppl. 1):226.
