Beta-adrenergic receptor antagonist antihypertensive medications impair arousal-induced modulation of working memory in Elderly Humans

Abstract

It is well-established that administration of moderate doses of the adrenal catecholamines epinephrine or norepinephrine shortly after training results in the enhancement of later retention performance in laboratory animals. these substances, released endogenously as a result of arousal, are thought to modulate memory processes by stimulating peripheral receptors that send neural messages to the brain, thus altering the memory storage process. The applicability of this hypothesis to the modulation of memory processes in humans was tested in this experiment by using elderly subjects who were chronically taking beta-receptor antagonist medications to control hypertension. A moderate level of muscle-tension-induced arousal was produced by having subjects squeeze a hand dynamometer during the initial storage and recall of highlighted words in short 200-word paragraphs. Twenty young normal individuals, 22 normotensive elderly subjects, 21 elderly subjects taking either calcium-channel blockers or angiotensin-converting enzyme inhibitors to control hypertension, and 21 elderly subjects taking beta-blocker antihypertensive medications served as subjects. The young subjects, normal elderly subjects, and those taking non-beta-blocker medications all showed enhanced long-term recognition performance as a result of the arousal manipulation. However, those subjecs chronically taking beta-receptor-antagonist medications showed no enhancement of memory. These findings provide support for the hypothesis that physiological arousal is an important modulator of memory and that adrenal catecholamine, systems are likely to mediate this effect. Further, this study indicates that elderly individuals taking beta-blocker medications may be less able to benefit from the normal memory modulating effects of arousal. Finally, these findings suggest that similar mechanisms modulate both declarative verbal memory in humans and conditioned avoidance learning in laboratory animals.