The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys
The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys
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DOI：
10.1016/j.biopsych.2005.05.022
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发表时间：
2005-12-01
影响因子：
10.6
通讯作者：
Arnsten, AFT
中科院分区：
文献类型：
--
作者：
Ramos, BP;Colgan, L;Arnsten, AFT
Background: Previous studies have indicated that beta adrenoergic receptor stimulation has no effect on the cognitive functioning of the prefrontal cortex (PFC). Blockade of beta-1 and beta-2 receptors in the PFC with the mixed beta-1/beta-2 antagonist, propanolol had no effect on spatial working memory performance. However, more selective blockade of beta-1 or beta-2 might show efficacy if the two receptors have opposite effects on the PFC function. The current study examined the effects of the selective beta-1 antagonists, betaxolol, on working memory in rats and monkeys.Methods: In rats, betaxolol (.0011-1.11 mu g/.5 mu L) was infused into the into PFC 5 min before delayed alternation testing. Monkeys were systemically injected with betaxolol (.0000011-.11 mg/kg) 2 hours before delayed response testing.Results: Betaxolol produced a doserelated improvement in working memory performance following either direct PFC infusion in rats or systemic administration in monkeys. However, some aged monkeys developed serious pancreatic problems over the course of this study.Conclusion: These findings suggest that endogenous activation of the beta-1 adrenergic receptor impairs PFC cognitive funtion. These results may have therapeutic relevance to post-traumatic stress disorder or other disorders with excessive noradrenergic activity and PFC dysfunction. Pancreatic side effects in ages subjects taking betaxolol further investigation.
