Activities of the principal brain vesicular monamine transporter, VMAT2, are key to understanding the cellular compartmentalization of monoamines. They may play key roles in modulating the actions and neurotoxicities induced by amphetamine and by each of the toxins that selectively kills dopaminergic neurons to provide the best current models of Parkinson's disease. They could even play roles in normal age-related alterations in these systems. In this year, workers in this Branch continued to describ the poperties of knockout mice with deletions of the VMAT2 gene and other plasma membrane monaamine transporters. Aging studies documented clear reductions in locomotion, in amphetamine responsiveness and exaggerated age-related losses of dopaminergic markers in the heterozygous VMAT2 knockouts. Mice with deletions of VMAT2 and the plasma membrane transporters for DAT and SERT are viable and fertile and may display altered amphetamine responses. VMAT2 knockout mice continue to substantially enhance our understanding of mechanisms of age- related alterations in dopaminergic systema and actions of psychostimulants and locomotor systems.
