title: Working memory deficits in transgenic rats overexpressing human adenosine A2A receptors in the brain.
abstract: Adenosine receptors in the central nervous system have been implicated in the modulation of different behavioural patterns and cognitive functions although the specific role of A(2A) receptor (A(2A)R) subtype in learning and memory is still unclear. In the present work we establish a novel transgenic rat strain, TGR(NSEhA2A), overexpressing adenosine A(2A)Rs mainly in the cerebral cortex, the hippocampal formation, and the cerebellum. Thereafter, we explore the relevance of this A(2A)Rs overexpression for learning and memory function. Animals were behaviourally assessed in several learning and memory tasks (6-arms radial tunnel maze, T-maze, object recognition, and several Morris water maze paradigms) and other tests for spontaneous motor activity (open field, hexagonal tunnel maze) and anxiety (plus maze) as modification of these behaviours may interfere with the assessment of cognitive function. Neither motor performance and emotional/anxious-like behaviours were altered by overexpression of A(2A)Rs. TGR(NSEhA2A) showed normal hippocampal-dependent learning of spatial reference memory. However, they presented working memory deficits as detected by performance of constant errors in the blind arms of the 6 arm radial tunnel maze, reduced recognition of a novel object and a lack of learning improvement over four trials on the same day which was not observed over consecutive days in a repeated acquisition paradigm in the Morris water maze. Given the interdependence between adenosinic and dopaminergic function, the present results render the novel TGR(NSEhA2A) as a putative animal model for the working memory deficits and cognitive disruptions related to overstimulation of cortical A(2A)Rs or to dopaminergic prefrontal dysfunction as seen in schizophrenic or Parkinson's disease patients.
authors.affiliation: Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neuroscience, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Giménez-Llort
authors.forename: Serge N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Shmidt
authors.forename: Laia
authors.initials: L
authors.lastname: Canela
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Camón
authors.forename: Monica
authors.initials: M
authors.lastname: Wassholm
authors.forename: Meritxell
authors.initials: M
authors.lastname: Canals
authors.forename: Anton
authors.initials: A
authors.lastname: Terasmaa
authors.forename: Albert
authors.initials: A
authors.lastname: Fernández-Teruel
authors.forename: Adolf
authors.initials: A
authors.lastname: Tobeña
authors.forename: Elena
authors.initials: E
authors.lastname: Popova
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Luigi
authors.initials: L
authors.lastname: Agnati
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Emili
authors.initials: E
authors.lastname: Martínez
authors.forename: Jörgen
authors.initials: J
authors.lastname: Scheel-Kruger
authors.forename: Carmen
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001007:Anxiety / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D008570:Memory, Short-Term / Q000502:physiology*; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D043705:Receptor, Adenosine A2A; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2; D018094:Receptors, Metabotropic Glutamate