The DAT knockdown mice have a hyperdopaminergic tone.
(a) Cyclic voltammetry was used to record dopamine
efflux in the striatum (n = 4 for each genotype).
Dopamine release was evoked by a single electrical pulse, applied at
the time indicated by the arrow. Extracellular dopamine was sampled
every 100 ms. The rising portion of the curve represents mainly
release, whereas the falling portion represents clearance via the DAT.
Release and clearance parameters were obtained by fitting recordings to
a Michaelis–Menten-based kinetic model. (Inset)
Representative cyclic voltammograms (current/voltage curves).
(b) The basal level of extracellular dopamine
concentration was measured by quantitative in vivo
microdialysis on freely moving animals in their home cages
(n = 4 for each genotype). The extracellular
dopamine concentration is significantly higher in knockdown than in
wild-type mice (t = 3.0, P =
0.02). (c) Total tissue (n = 4 for
each genotype) content of dopamine and its metabolites were measured by
HPLC-coupled electrochemical detection. DOPAC/dopamine and
HVA/dopamine ratios were used as an index of dopamine turnover. Both
DOPAC/dopamine (t = 3.7, P =
0.01) and HVA/dopamine (t = 8.0,
P = 0.0002) ratios were significantly higher in
knockdown than in wild-type mice. Error bar represents SEM.