Page - (000136) - in Biomedical Chemistry: Current Trends and Developments

LC-NE system stimulates the HPA axis and the sympathetic nervous system while hindering neurovegetative functions and the parasympathetic nervous system (reviewed in Aston-Jones, 1996). The LC promotes survival during a crisis by favoring fast and simpler responses through inhibition of frontal cortex functions (Arnsten, 2000) and via the amygdala and other CNS structures that encode aversive memories. LC neurons discharge in 2 types of modes: tonic and phasic to modulate attention and behavior (Aston-Jones & Cohen, 2005). The effects of CRH or stressors not only increases LC activity but also modify LC discharge toward the tonic mode; this shift in discharge style is attenuated by CRH antagonism or by opiate antagonism and the combined removal of CRH and opioid actions rendered the LC activity resistant to the effects of the stressor (Curtis, 2012). Stress-induced LC activation increasing arousal but could also facilitate behavioral flexibility during threatening situations (Snyder, 2012). The amygdala can also modulate hypothalamic CRH release and autonomic centers in the brainstem to respectively increase HPA axis and LC-NE system activities while inhibiting the prefrontal cortex (Cahill & McGaugh, 1998). Neurons in the hypothalamus, LC and amygdala contain multiple feed-forward connections that can promote a robust and persistent stress response. The dorsolateral prefrontal cortex is implicated in cognition and attention, and the ventromedial prefrontal cortex regulates affect, neuroendocrine, and autonomic activities [reviewed in (Arnsten, 2000; Fuster, 2000, 2001; Smith & Jonides, 1999)]. Cortical lesions in humans and rodents cause exaggerated autonomic and endocrine responses; thus, there is a reciprocal inhibitory relationship between the prefrontal cortex inhibiting the stress system, in which they can inhibit the activity of each other (Fuster, 2000, 2001; Smith & Jonides, 1999), and activation of the prefrontal cortex and consequent restraint of the stress and the sympathetic nervous systems promote flexibility in cognition and affect (Smith & Jonides, 1999). 2.2.2.3 The Immune System