title: Loss of NMDA receptors in dopamine neurons leads to the development of affective disorder-like symptoms in mice.
abstract: The role of changes in dopamine neuronal activity during the development of symptoms in affective disorders remains controversial. Here, we show that inactivation of NMDA receptors on dopaminergic neurons in adult mice led to the development of affective disorder-like symptoms. The loss of NMDA receptors altered activity and caused complete NMDA-insensitivity in dopamine-like neurons. Mutant mice exhibited increased immobility in the forced swim test and a decrease in social interactions. Mutation also led to reduced saccharin intake, however the preference of sweet taste was not significantly decreased. Additionally, we found that while mutant mice were slower to learn instrumental tasks, they were able to reach the same performance levels, had normal sensitivity to feedback and showed similar motivation to exert effort as control animals. Taken together these results show that inducing the loss of NMDA receptor-dependent activity in dopamine neurons is associated with development of affective disorder-like symptoms.
authors.affiliation: Laboratory of Transgenic Models, Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Jastrzębska
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Walczak
authors.affiliation: Laboratory of Transgenic Models, Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland.
authors.forename: Przemysław Eligiusz
authors.initials: PE
authors.lastname: Cieślak
authors.affiliation: Laboratory of Transgenic Models, Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Szumiec
authors.affiliation: Laboratory of Transgenic Models, Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Turbasa
authors.affiliation: Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85, Linköping, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Engblom
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Błasiak
authors.affiliation: Laboratory of Transgenic Models, Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland.
authors.forename: Jan Rodriguez
authors.initials: JR
authors.lastname: Parkitna
mesh_terms: D000341:Affective Disorders, Psychotic / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate