Decreased exploratory activity and impaired passive avoidance behaviour inmice deficient for the alpha(1b)-adrenoceptor

There is growing evidence that a dysfunction of central noradrenergic neuro transmission is involved in age-related impairments of cognitive performanc e and the pathophysiology of Alzheimer's disease (AD). A reduction of densi ty of central alpha (1)-adrenergic receptors (alpha (1)-AR) has been shown in aging and AD brains. Three alpha (1)-AR subtypes (alpha (1a), alpha (1b) and alpha (1d)) have been identified by molecular cloning. However, very l ittle is known about the functional role of distinct alpha (1)-AR subtypes in the brain. This problem was specifically addressed using a model of knoc kout mouse deficient in alpha (1b)-AR (alpha (1B)-/-) because these animals show a 40% reduction of alpha (1)-AR density in the brain as already repor ted. In comparison to the wild-type mice (alpha (1B)+/+), alpha (1B)-/- mic e showed significantly reduced square entries and a reduced rearing behavio ur was observed over all sessions in the open field. In passive avoidance p rocedures, alpha (1B)-/- mice showed a tendency towards decreased short-ter m-latency and a significant decline in long-term-latency. The present resul ts indicate that mutation of a single member of the alpha (1)-AR gene famil y creates a distinct phenotype and provide evidence that alpha (1B)-AR is p ossibly involved in modulation of memory consolidation and fear-motivated e xploratory activity. Furthermore, this model of knockout mice may be useful in elucidating the role of alpha (1B)-AR in dementias involving deficits o f the noradrenergic system. (C) 2000 Published by Elsevier Science B.V.