Evidence for impaired function of dopaminergic system in Wfs1-deficient mice.

Abstract:

:Immunohistological studies suggest abundant expression of Wfs1 protein in neurons and nerve fibers that lie in the vicinity of dopaminergic (DA-ergic) fibers and neurons. Therefore, we sought to characterize the function of DA-ergic system in Wfs1-deficient mice. In wild-type mice, amphetamine, an indirect agonist of DA, caused significant hyperlocomotion and increase in tissue DA levels in the dorsal and ventral striatum. Both effects of amphetamine were significantly blunted in homozygous Wfs1-deficient mice. Motor stimulation caused by apomorphine, a direct DA receptor agonist, was somewhat stronger in Wfs1-deficient mice compared to their wild-type littermates. However, apomorphine caused a similar reduction in levels of DA metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the dorsal and ventral striatum in all genotypes. Behavioral sensitization to repeated treatment with amphetamine (2.5 mg/kg) was observed in wild-type, but not in Wfs1-deficient mice. The expression of DA transporter gene (Dat) mRNA was significantly lower in the midbrain of male and female homozygous mice compared to wild-type littermates. Altogether, the blunted effects of amphetamine and the reduced gene expression of DA transporter are probably indicative of an impaired functioning of the DA-ergic system in Wfs1-deficient mice.

journal_name

Behav Brain Res

authors

Visnapuu T,Plaas M,Reimets R,Raud S,Terasmaa A,Kõks S,Sütt S,Luuk H,Hundahl CA,Eskla KL,Altpere A,Alttoa A,Harro J,Vasar E

doi

10.1016/j.bbr.2013.01.046

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

90-9

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(13)00073-9

journal_volume

244

pub_type

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