Laboratory of Cellular and Synaptic Physiology, University of Texas at Dallas, School for Behavioral and Brain Sciences, Richardson, TX 75080, USA.
Neuropharmacology. 2012 Jun;62(7):2178-83. doi: 10.1016/j.neuropharm.2011.12.024. Epub 2012 Jan 2.
Numerous studies have suggested a facilitatory role of the noradrenergic system in attention. Cognitive functions relating to attentive states--arousal, motivation, behavioral flexibility, and working memory--are enhanced by norepinephrine release throughout the brain. The present study addresses the role of the adrenergic system on stimulus validity and sustained attention within the auditory system. We examined the effects of adrenoceptor stimulation via systemic injection of α1 and α2-adrenoceptor antagonist and agonist drugs, prazosin (1 mg/kg), phenylephrine (0.1 mg/kg), yohimbine (1 mg/kg), and clonidine (0.0375 mg/kg), respectively. Our results indicate that α1-adrenergic stimulation is ineffective in modulating the biological assessment of auditory signal validity in the non-stressed rat, while α2-adrenoceptor antagonist and agonist drugs were effective in modulating both accuracy and response latencies in the habituated animal. Remarkably, blockade of α2-adrenoceptors significantly improved the animal's ability to correctly reject non-signal events. These findings indicate not only a state dependent noradrenergic component of auditory attentional processing, but a potential therapeutic use for drugs targeting norepinephrine release in neurological disorders ranging from Alzheimer's disease to schizophrenia.
许多研究表明，去甲肾上腺素系统在注意力中起着促进作用。与注意力状态相关的认知功能——觉醒、动机、行为灵活性和工作记忆——通过整个大脑的去甲肾上腺素释放而增强。本研究探讨了肾上腺素系统在听觉系统中的刺激有效性和持续注意力中的作用。我们通过系统注射 α1 和 α2-肾上腺素受体拮抗剂和激动剂药物（特拉唑嗪（1 毫克/千克）、苯肾上腺素（0.1 毫克/千克）、育亨宾（1 毫克/千克）和可乐定（0.0375 毫克/千克）来检查肾上腺素受体刺激的影响。我们的结果表明，α1-肾上腺素刺激在调节非应激大鼠听觉信号有效性的生物评估方面无效，而 α2-肾上腺素受体拮抗剂和激动剂药物在调节习惯化动物的准确性和反应潜伏期方面均有效。值得注意的是，α2-肾上腺素受体阻断剂显著提高了动物正确拒绝非信号事件的能力。这些发现不仅表明了听觉注意力处理中存在依赖于状态的去甲肾上腺素成分，而且还表明了针对从阿尔茨海默病到精神分裂症等神经疾病中去甲肾上腺素释放的药物具有潜在的治疗用途。
