title: Characteristics of behavioral abnormalities in alpha1d-adrenoceptors deficient mice.
abstract: To investigate the functional role of alpha1d-adrenergic receptor (alpha1d-AR) in the CNS, we have generated mutant mice lacking the alpha1d-AR using a gene targeting approach and examined in detail the effects of alpha1d-AR knockout mice on motor function, sensory function, and learning and memory. alpha1d-AR knockout mice showed better motor coordination at the highest rotating speed of the rotarod performance and stronger muscle tone using the traction meter, but their locomotor activity and swimming ability in the water maze were not affected. In the water maze requiring reference memory, alpha1d-AR knockout mice showed normal spatial learning. In the Y-maze task requiring working memory or attention, alpha1d-AR knockout mice displayed an impaired spontaneous alternation performance. The alpha1d-AR knockout mice tended to display lower levels of acoustic startle responses than the wild-type group at lower pulse intensities, although the acoustic prepulse inhibition was not impaired in the alpha1d-AR knockout mice. Furthermore, the NMDA receptor antagonist, MK-801-induced deficits of acoustic prepulse inhibition were not observed in the alpha1d-AR knockout mice. These results clearly demonstrate that the alpha1d-AR receptor plays an important role in the process of auditory sensory function, attention or working memory rather than reference memory, and the sensorimotor gating deficits induced by the NMDA receptor antagonist.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka 814-0180, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tsuda
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hasebe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fukue
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takano
authors.forename: Hiro-O
authors.initials: HO
authors.lastname: Kamiya
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000502:physiology; D001523:Mental Disorders / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D012022:Reflex, Acoustic / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D018340:Receptors, Adrenergic, alpha-1