Decreased exploratory activity and impaired passive avoidance behaviour in mice deficient for the α1b-adrenoceptor

There is growing evidence that a dysfunction of central noradrenergic neurotransmission is involved in age-related impairments of cognitive performance and the pathophysiology of Alzheimer's disease (AD). A reduction of density 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 little is known about the functional role of distinct alpha (1)-AR subtypes in the brain. This problem was specifically addressed using a model of knockout 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 reported. In comparison to the wild-type mice (alpha (1B)+/+), alpha (1B)-/- mice showed significantly reduced square entries and a reduced rearing behaviour was observed over all sessions in the open field. In passive avoidance procedures, alpha (1B)-/- mice showed a tendency towards decreased short-term-latency and a significant decline in long-term-latency. The present results indicate that mutation of a single member of the alpha (1)-AR gene family creates a distinct phenotype and provide evidence that alpha (1B)-AR is possibly involved in modulation of memory consolidation and fear-motivated exploratory activity. Furthermore, this model of knockout mice may be useful in elucidating the role of alpha (1B)-AR in dementias involving deficits of the noradrenergic system. (C) 2000 Published by Elsevier Science B.V.