VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity

摘要

The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkin- sonism-inducing dopamine neurotoxins such as 1-methyl-4- phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP+ each also act at nonvesicu- lar sites, providing current uncertainties about the contribu- tions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resis- tance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice.