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Aging effects on locomotor activity in dopamine transporter and vesicular monoamine transporter knockout mice



Aging effects on locomotor activity in dopamine transporter and vesicular monoamine transporter knockout mice



Society for Neuroscience Abstracts 26(1-2): Abstract No -344 5



Dopamine is both a neurotransmitter important for regulating locomotor activities and a potential age-related oxidative toxin. Dopamine is compartmentalized to more- and less- sensitive cellular compartments by the plasma membrane DAT and vesicular membrane VMAT2 transporters that pump dopamine into neuronal cytoplasm and into synaptic vesicles, respectively. We have assessed possible roles for variations in levels of DAT and VMAT2 expression on the declines in locomotor activities that accompany the losses of dopaminergic systems in normal aging. We have measured basal and amphetamine-stimulated locomotor activities in VMAT2 and DAT heterozygotes and littermate wild-type control of varying ages. Aging produced larger decreases in baseline- and saline-stimulated locomotion and amphetamine-stimulated stereotypy in VMAT2 heterozygotes than in wild-type. DAT heterozygotes did not show such decreases. This effect of reduced VMAT2 expression, not found with reduced DAT expression, is consistent with the idea that higher levels of extravesicular, cytoplasmic dopamine could contribute to aging dopaminergic systems important for locomotor control.

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