title: Alpha2C-adrenoceptor-overexpressing mice are impaired in executing nonspatial and spatial escape strategies.
abstract: Drugs acting via alpha2-adrenoceptors modulate cognitive functions mediated via frontostriatothalamic feedback loops. The alpha2C-adrenoceptor subtype is expressed in the basal ganglia, hippocampus, and neocortex, areas that are involved in memory and other cognitive functions. alpha2C-Overexpressing (OE) mice were impaired in spatial or nonspatial water maze (WM) tests, and alpha2 antagonist treatment fully reversed the WM escape defect in OE mice. However, alpha2C-overexpression did not influence open field and passive avoidance behaviors or cortical EEG arousal or the actions of alpha2 agonist or antagonist drugs on these functions. Our results suggest that alpha2C-adrenoceptors can modulate navigation to a hidden or visible escape platform, whereas many other actions of alpha2-adrenergic agents, such as sedation, are not mediated via alpha2C-adrenoceptors. Therefore, alpha2-agonists lacking alpha2C-AR affinity or alpha2C-AR subtype-selective alpha2 antagonists could modulate functioning of frontostriatothalamic feedback loops more effectively than the current subtype-nonselective drugs.
authors.affiliation: Department of Neurology and Neuroscience, University of Kuopio, Kuopio, FIN-70211, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Björklund
authors.forename: J
authors.initials: J
authors.lastname: Sirviö
authors.forename: J
authors.initials: J
authors.lastname: Puoliväli
authors.forename: J
authors.initials: J
authors.lastname: Sallinen
authors.forename: P
authors.initials: P
authors.lastname: Jäkälä
authors.forename: M
authors.initials: M
authors.lastname: Scheinin
authors.forename: B K
authors.initials: BK
authors.lastname: Kobilka
authors.forename: P
authors.initials: P
authors.lastname: Riekkinen
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D020926:Medetomidine; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity
chemical_list: C547775:Adra2c protein, mouse; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D020926:Medetomidine