“…Studies of mice lacking VMAT2 show that the homozygote animals die within a few days of birth and heterozygotes have significantly decreased monoamine levels and increased neurotoxicity as well as depressive-like phenotypes (Fon et al, 1997, Takahashi et al, 1997, Wang et al, 1997, Fumagalli et al, 1999, Narboux-Neme et al, 2011). Numerous other preclinical studies have shown that drugs of abuse have robust effects on VMAT2 function/expression, including increased neurotoxicity after methamphetamine exposure (Fumagalli et al, 1999, Uhl et al, 2000, Hall et al, 2003, Savelieva et al, 2006, Fleckenstein et al, 2007, Vergo et al, 2007, Yamamoto et al, 2007, Tong et al, 2008, Fleckenstein et al, 2009, Eiden and Weihe, 2011, Ellis et al, 2011, McFadden et al, 2011a, McFadden et al, 2011b, Vieira-Brock et al, 2011). Caudle et al (2007) observed that mice expressing approximately 5% of normal VMAT2 (VMAT2 LO) display age-associated nigrostriatal dopamine dysfunction accompanied by increased oxidative stress and decreased expression of the dopamine transporter and tyrosine hydroxylase, ultimately leading to neurodegeneration (Caudle et al, 2007).…”