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Increased striatal dopamine release and hyperdopaminergic‐like behaviour in mice lacking both alpha‐synuclein and gamma‐synuclein
Author(s) -
Senior Steven L.,
Ninkitalia,
Deacon Robert,
Bannerman David,
Buchman Vladimir L.,
Cragg Stephanie J.,
WadeMartins Richard
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06055.x
Subject(s) - reuptake , dopamine transporter , dopamine , alpha synuclein , striatum , medicine , endocrinology , neuroscience , dopamine plasma membrane transport proteins , biology , null allele , chemistry , parkinson's disease , phenotype , receptor , biochemistry , serotonin , disease , dopaminergic , gene
Alpha‐synuclein is intimately involved in the pathogenesis of Parkinson's disease, and has been implicated in the regulation of synthesis, release and reuptake of dopamine (DA). However, mice lacking members of the synuclein family have been reported to display no overt behavioural phenotype. This may be a result of compensatory upregulation of other synucleins during development. Here we report on behaviour and DA synapse function of alpha‐synuclein null, gamma‐synuclein null, and alpha‐gamma‐synuclein double‐null knockout mice. Double‐null mice were hyperactive in a novel environment and alternated at a lower rate in a T‐maze spontaneous alternation task, a phenotype reminiscent of mice expressing reduced levels of the DA transporter. To investigate a possible hyperdopaminergic phenotype in alpha‐gamma‐synuclein double‐null mice, we used fast‐scan cyclic voltammetry at carbon‐fibre microelectrodes to assess DA release and reuptake in striatal slices from wild‐type, alpha‐null, gamma‐null and double‐null mice in real time. Double‐null mice were found to have a twofold increase in the extracellular concentration of DA detected after discrete electrical stimuli in the striatum. By measuring the rate of reuptake of DA and tissue DA content in these animals, we showed that the observed increase in size of striatal DA transients was not attributable to a decrease in reuptake of DA via the DA transporter, and can not be attributed to an increase in tissue DA levels in the striatum. Rather, we propose that loss of both alpha‐ and gamma‐synuclein causes an increase in release probability from dopaminergic synapses.