Subchronic treatment with prazosin improves passive avoidance learning in aged mice: possible relationships to alpha(1)-receptor up-regulation

While many evidences indicate that deficits of central noradrenergic neurot ransmission are involved in the age-related decline of cognitive functions in animals and man, very little is known about the specific role of central alpha (1)-adrenergic receptors. Therefore, this problem was specifically a ddressed in the present communication using the alpha (1)-adrenoceptor anta gonist prazosin as pharmacological tool. While the acute administration of prazosin did not affect passive avoidance learning of young or aged mice, a n improvement of learning capabilities was seen after subchronic treatment, but for the aged animals only. An U-shaped dose response curve was seen. 0 .3 mg/kg prazosin was most effective. Very interestingly, only for this dos e a significant up-regulation of the density of alpha (1)-adrenoceptors in the mouse brain was found in the aged animals only. The data suggest a poss ible causal relationship between effects of prazosin on passive avoidance l earning and central alpha (1)-receptor density.