Characteristics of behavioral abnormalities in α 1d-adrenoceptors deficient mice

Abstract

To investigate the functional role of α 1d-adrenergic receptor (α 1d-AR) in the CNS, we have generated mutant mice lacking the α 1d-AR using a gene targeting approach and examined in detail the effects of α 1d-AR knockout mice on motor function, sensory function, and learning and memory. α 1d-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, α 1d-AR knockout mice showed normal spatial learning. In the Y-maze task requiring working memory or attention, α 1d-AR knockout mice displayed an impaired spontaneous alternation performance. The α 1d-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 α 1d-AR knockout mice. Furthermore, the NMDA receptor antagonist, MK-801-induced deficits of acoustic prepulse inhibition were not observed in the α 1d-AR knockout mice. These results clearly demonstrate that the α 1d-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.