title: Adult neurogenesis reduction by a cytostatic treatment improves spatial reversal learning in rats.
abstract: Adult neurogenesis in the dentate gyrus adds a substantial number of new functional neurons to the hippocampus network in rodents. To date, however, the function of these new granule cells remains unclear. We conducted an experiment to assess the contribution of adult neurogenesis in the dentate gyrus to acquisition and reversal learning in a task that predominantly requires generalization of a rule. Young adult male Long-Evans rats were repeatedly administered either a cytostatic temozolomide or saline for a period of four weeks (3 injections per week). Post treatment, animals were injected with bromodeoxyuridine to quantify adult neurogenesis in the dentate gyrus. For behavioral assessment we used hippocampus-dependent active place avoidance with reversal in a Carousel maze. Animals first learned to avoid a 60° sector on the rotating arena. Afterwards, sector was relocated to the opposite side of the rotating arena (reversal). The administration of temozolomide significantly improved the reversal performance compared to saline-treated rats. Our results suggest a significant, level-dependent, improvement of reversal learning in animals with reduced adult neurogenesis in hippocampus.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Electronic address: hana.brozka@fgu.cas.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Brozka
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Electronic address: adela.pistikova@fgu.cas.cz.
authors.forename: Adela
authors.initials: A
authors.lastname: Pistikova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Dominika
authors.initials: D
authors.lastname: Radostova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Vales
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Svoboda
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; CRTD-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Grzyb
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Electronic address: ales.stuchlik@fgu.cas.cz.
authors.forename: Ales
authors.initials: A
authors.lastname: Stuchlik
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012193:Reversal Learning / Q000187:drug effects*; D065853:Spatial Learning / Q000187:drug effects*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Active avoidance; Adult neurogenesis; Discrimination; Generalization; Hippocampus; Reversal