Ramos BP, Arnsten AF. Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 113: 523-536

Department Neurobiology, Yale Medical School, New Haven, CT 06520-8001, USA.
Pharmacology [?] Therapeutics (Impact Factor: 9.72). 04/2007; 113(3):523-36. DOI: 10.1016/j.pharmthera.2006.11.006
Source: PubMed


Norepinephrine (NE) has widespread projections throughout the brain, and thus, is ideally positioned to orchestrate neural functions based on arousal state. For example, NE can increase "signal/noise" ratio in the processing of sensory stimuli, and can enhance long-term memory consolidation in the amygdala and hippocampus through actions at alpha-1 and beta adrenoceptors. Over the last 20 years, NE has also been shown to play a powerful role in regulating the working memory and attention functions of the prefrontal cortex (PFC). Moderate levels of NE released under control conditions strengthen prefrontal cortical functions via actions at post-synaptic alpha-2A adrenoceptors with high affinity for NE, while high levels of NE release during stress impair PFC cortical functions via alpha-1 and possibly beta-1 receptors with lower affinity for NE. Thus, levels of NE determine whether prefrontal cortical or posterior cortical systems control our behavior and thought. Understanding these receptor mechanisms has led to new intelligent treatments for neuropsychiatric disorders associated with PFC dysfunction.

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    • "At moderate levels of increase, neural activity in PFC is high and executive function abilities are maximized. As these neurochemicals continue to rise beyond a moderate level, however, activity in PFC is reduced and activity is increased in brain areas associated with reactive motoric and emotional-motivational responses to stimulation (Ramos & Arnsten 2007). "
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    • "Under physiological conditions, cortisol, in conjunction with epinephrine and norepinephrine, prepares an individual for the " fight or flight response " , enabling rapid shifting of blood flow toward large skeletal muscles and permitting an individual to flee threatening situations. Cortisol also plays a significant role in memory processes (Tollenaar et al., 2009), with areas of the brain important for memory (e.g., hippocampus, prefrontal cortex, amygdala) expressing high levels of GC receptors (Ramos and Arnsten, 2007). In the hippocampal region, excessive GCs levels have been linked to a significant reduction in neurogenesis (Liu et al., 2003), suppression of LTP in excitatory synapses (Setiawan et al., 2007), cell death through apoptosis (Zhao et al., 2007), and extensive dendritic reorganization in the prefrontal cortex (Cook and Wellman, 2004). "
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    • "Third, chronic as well as acute stress – in addition to its well established effects on hippocampus-dependent declarative memory – exerts strong effects on cognitive control processes, presumably via influences of stress hormones and catecholamines (noradrenaline, dopamine) on prefrontal neurotransmission (for review see Arnsten, 2009). These stress-related modulations appear to induce a shift of behavioural control from a goal-directed ( " top-down " ) to an affective-habitual ( " bottom-up " ) mode dominated by the amygdale and basal ganglia (Ramos and Arnsten, 2007; Wang et al., 2007; Wingard and Packard, 2008). In addition, recent evidence indicates that acute social stress also shifts the balance between cognitive flexibility and stability towards increased tonic goal shielding and reduced context-sensitive adaptation of cognitive control (Plessow et al., 2011a, 2011b). "
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