The Role of the Brain's Chemical production during stressful situations

The brain noradrenergic system is activated by acute stress. The post-synaptic effects of norepinephrine (NE), exerted at a cellular or
neural circuit level, have been described as modulatory in nature, as NE facilitates responses evoked in target cells by both excitatory and
inhibitory afferent input. Over the past few years, we have undertaken a series of studies to understand how these cellular modulatory effects
of NE, elicited by acute stress, might translate into modulation of the behavioral–affective components of the whole-animal response to
stress. Using microdialysis, we have demonstrated that acute immobilization stress activates NE release in a number of stress-related limbic
forebrain target regions, such as the central and medial amygdala, lateral bed nucleus of the stria terminalis, medial prefrontal cortex, and
lateral septum. Using microinjections of adrenergic antagonist drugs directly into these regions, we have shown that this stress-induced release
of NE facilitates a number of anxiety-like behavioral responses that are mediated in these regions, including stress-induced reduction of openarm
exploration on the elevated plus-maze, stress-induced reduction of social interaction behavior, and activation of defensive burying
behavior by contact with an electrified probe. Dysregulation of the brain noradrenergic system may be a factor in determining vulnerability to
stress-related pathology, or in the interaction of genetic vulnerability and environmental sensitization. Compared to outbred Sprague–Dawley
rats, we have shown that the modulatory effect of NE is deficient in Wistar–Kyoto rats, which also exhibit attenuated behavioral reactivity to
acute stress, as well as increased vulnerability to stress-induced gastric ulcers and exaggerated activation of the hypothalamic–pituitary–
adrenal (HPA) stress axis. Further, repeated exposure to mild intermittent cold stress resulted in a much greater sensitization of both the brain
noradrenergic system and the HPA axis in Wistar–Kyoto rats compared to Sprague–Dawley rats. The recruitment of a robust noradrenergic
facilitatory influence following repeated cold exposure in this previously deficient strain resulted in an aberrant HPA response, which may be
illustrative of the kinds of neurobiological changes that may contribute to the development of stress-related neuropsychiatric disorders such as
depression, post-traumatic stress disorder, or other anxiety disorders in predisposed or susceptible individuals. On the other side of the same
issue, regulatory alterations in noradrenergic neurotransmission, or in the stress-modulatory functions of NE, may be important in the
behavioral effects of chronic antidepressant drug treatment. We present recent preliminary results addressing the effects of chronic treatment
with the selective NE reuptake inhibitor, desipramine, on acute behavioral reactivity to stress. A better understanding of the role of NE in
adaptive responses to acute stress, the pathological consequences of prolonged, repeated or severe stress, and the mechanisms of action of
drugs used to treat stress-related diseases, may contribute to the future development of more effective strategies for the treatment or even
prevention of such disorders.