title: The role of the alpha 2A-adrenoceptor in mouse stress-coping behaviour.
abstract: Acute stress is known to impair memory functions in both men and laboratory rodents. In human the alpha 2A-adrenoceptor system is known to play a critical role in regulating acute neuropsychological stress responses and, ultimately, stress-coping behaviour. In search for neurobiological and central nervous mechanisms behind these behaviours we investigated if the alpha 2A-adrenoceptor is involved in these mechanisms in mice. Phenotypical differences between the A/J and C57BL/6J (B6) mouse inbred strains were evaluated in previous studies. These data showed significant strain differences in various motivational systems (anxiety, exploration, locomotion, memory etc.). From the literature it is known that chromosome 19 contains the gene for the adrenergic alpha 2A receptor that is thought to be involved in emotional behaviours, among others anxiety-related avoidance behaviour and arousal. We investigated if this pathway could possibly be involved in avoidance/arousal susceptibility by applying an agonist (dexmedetomidine) and an antagonist (atipamezole) of the alpha 2A-adrenoceptor to male mice from a consomic strain (C57BL/6J-Chr 19(A)/NaJ, abbreviated to CSS19=anxious), and the corresponding donor (A/J=anxious) and host (B6=non-anxious) strains. The mice were tested in the modified hole board (mHB) test which allows for the assessment of a variety of behavioural patterns by use of only one test. In addition, a forced swimming test (FST) was conducted to test for stress-coping behaviour. Results of the behavioural testing in the mHB-test showed significant strains differences and strain-specific treatment effects for parameters describing anxiety-related endophenotypes. The FST revealed effects of dexmedetomidine and atipamezole on stress-coping behaviour. In conclusion, the involvement of the alpha 2A-adrenoceptor, located on mouse chromosome 19, on anxiety-related behaviour remains unclear and will possibly not play a main role in the development of anxiety-related behaviour in mice. However, we could show involvement of this receptor in stress-coping behaviour in mice.
authors.affiliation: Department of Animals in Science & Society, Division of Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. m.c.laarakker@umcutrecht.nl
authors.forename: Marijke C
authors.initials: MC
authors.lastname: Laarakker
authors.forename: Jeroen R van
authors.initials: JR
authors.lastname: Raai
authors.forename: Hein A
authors.initials: HA
authors.lastname: van Lith
authors.forename: Frauke
authors.initials: F
authors.lastname: Ohl
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology*; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D020927:Dexmedetomidine / Q000494:pharmacology; D005106:Exploratory Behavior; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology* / Q000534:rehabilitation; D013550:Swimming / Q000502:physiology
chemical_list: C547768:ADRA2A protein, human; C547769:Adra2a protein, mouse; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D020927:Dexmedetomidine