| OCR Text |
Show 13 et al., 2002)). Together, these studies provide evidence that noradrenaline contributes to performance of prefrontal-mediated tasks requiring attention, working memory, and cognitive flexibility. The prefrontal cortex is sensitive to small changes in levels of noradrenaline, and too little or too much can weaken prefrontal control of behaviors (Brennan and Arnsten, 2008; Arnsten, 2009). For example, selective cortical depletion of noradrenaline impairs sustained attention (Milstein et al., 2007) and cognitive flexibility (Tait et al., 2007; McGaughy et al., 2008; Newman et al., 2008). On the other hand, direct infusion of the pharmacological stressor yohimbine (an α2 antagonist) into the prefrontal cortex impairs behavioral flexibility, working memory, and response inhibition (Li and Mei, 1994; Ma et al., 2003; Caetano, 2013). Acute psychosocial stress has similarly been found to impair working memory and activation of the prefrontal cortex in humans (Schoofs et al., 2008; Qin et al., 2009). Thus, enhanced noradrenergic signaling during acute stress can compromise prefrontal cortical-dependent cognition. While noradrenergic contributions to decision making, working memory, attention, and cognitive flexibility have been extensively studied, contributions to cognitive impulsivity have not been examined. Neuroimaging studies show that acute stress affects processing of risky outcomes and reward valuation in the prefrontal cortex in healthy human subjects (Ossewaarde et al., 2011; Mather and Lighthall, 2012; Treadway et al., 2013). Stress-induced changes in reward valuation may be particularly maladaptive in alcoholics. Specifically, acute stress may contribute to relapse by affecting the perceived value of immediate versus delayed rewards, leading to a bias for immediately available alcohol reinforcers at the expense of continued abstinence. Thus, the first goal of this project was to examine the effect of acute stress on cognitive impulsivity. Given the contributions of the noradrenergic system to decision making processes and reward valuation, the second goal of this project was to characterize the effect of additional noradrenergic receptor-specific manipulations on impulsivity. Here, I draw attention to propranolol, guanfacine, and prazosin, which have received attention as potential therapies to prevent stress-induced relapse. |
