title: Effect of GDNF on depressive-like behavior, spatial learning and key genes of the brain dopamine system in genetically predisposed to behavioral disorders mouse strains.
abstract: The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and brain dopamine system in predisposed to depressive-like behavior ASC (Antidepressant Sensitive Cataleptics) mice in comparison with the parental "nondepressive" CBA mice was studied. In 7days after administration (800ng, i.c.v.) GDNF decreased escape latency time and the path traveled to reach hidden platform in Morris water maze in ASC mice. GDNF enhanced depressive-like behavioral traits in both "nondepressive" CBA and "depressive" ASC mice. In CBA mice, GDNF decreased functional response to agonists of D1 (chloro-APB hydrobromide) and D2 (sumanirole maleate) receptors in tail suspension test, reduced D2 receptor gene expression in the substantia nigra and increased monoamine oxydase A (MAO A) gene expression in the striatum. GDNF increased D1 and D2 receptor genes expression in the nucleus accumbens of ASC mice but failed to alter expression of catechol-O-methyltransferase, dopamine transporter, MAO B and tyrosine hydroxylase genes in both investigated mouse strains. Thus, GDNF produced long-term genotype-dependent effect on behavior and the brain dopamine system. GDNF pretreatment (1) reduced D1 and D2 receptors functional responses and D2 receptor gene expression in s. nigra of CBA mice; (2) increased D1 and D2 receptor genes expression in n. accumbens of ASC mice and (3) improved spatial learning in ASC mice. GDNF enhanced depressive-like behavior both in CBA and ASC mice. The data suggest that genetically defined variance in the cross-talk between GDNF and brain dopamine system contributes to the variability of GDNF-induced responses and might be responsible for controversial GDNF effects.
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia. Electronic address: naumenko2002@mail.ru.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Naumenko
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Kondaurova
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Bazovkina
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Anton S
authors.initials: AS
authors.lastname: Tsybko
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Ilchibaeva
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Nikita V
authors.initials: NV
authors.lastname: Khotskin
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Alina A
authors.initials: AA
authors.lastname: Semenova
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
authors.forename: Nina K
authors.initials: NK
authors.lastname: Popova
mesh_terms: D000818:Animals; D001526:Behavioral Symptoms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D020022:Genetic Predisposition to Disease; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D019417:Hindlimb Suspension; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects*; D013550:Swimming / Q000523:psychology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; C000593198:COMT protein, mouse; D002394:Catechol O-Methyltransferase; D004298:Dopamine
keywords: D1 and D2 receptors functional response; D1 and D2 receptors, dopamine transporter, tyrosine hydroxylase genes expression; Depression; GDNF; Spatial learning