Decreased exploratory activity and impaired passive avoidance behaviour in mice deficient for the alpha(1b)-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.
Knauber
J
J
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Müller
W E
WE
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology*; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015999:Multivariate Analysis; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
C547717:Adra1b protein, mouse; D018340:Receptors, Adrenergic, alpha-1