title: 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.
authors: Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. tanel.visnapuu@ut.ee
authors: Tanel
authors: T
authors: Visnapuu
authors: Mario
authors: M
authors: Plaas
authors: Riin
authors: R
authors: Reimets
authors: Sirli
authors: S
authors: Raud
authors: Anton
authors: A
authors: Terasmaa
authors: Sulev
authors: S
authors: Kõks
authors: Silva
authors: S
authors: Sütt
authors: Hendrik
authors: H
authors: Luuk
authors: Christian Ansgar
authors: CA
authors: Hundahl
authors: Kattri-Liis
authors: KL
authors: Eskla
authors: Alina
authors: A
authors: Altpere
authors: Aet
authors: A
authors: Alttoa
authors: Jaanus
authors: J
authors: Harro
authors: Eero
authors: E
authors: Vasar
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D059333:Central Nervous System Sensitization / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D017448:Receptors, Dopamine D2; C114987:wolframin protein; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine