Stress-related activation of cerebral dopaminergic systems

The changes in dopamine catabolites in various regions of mouse brain have been studied following a variety of behavioral treatments. In confirmation of the results of many others, we find that treatments such as footshock or restraint result in a pronounced activation of dopaminergic systems in the prefrontal cortex, as determined by increases in the content of DOPAC (3,4-dihydroxyphenylacetic acid). However, we also find small but statistically significant increases of DOPAC in the hypothalamus and brain stem even with mild treatments. With restraint and more intense footshock we observe increases of DOPAC in all regions studied, including nucleus accumbens, olfactory tubercle, amygdala, and the striatum. Thus in contrast to previous reports, we find that the DA response in stress is global like that of norepinephrine [as determined by increases of 3-methoxy,4-hydroxyphenylethyleneglycol, (MHPG)], and not specific to the prefrontal cortex. The activation of prefrontal cortex DA metabolism is associated with an activation of the synthetic enzyme tyrosine hydroxylase. The response pattern of catecholamine metabolites is similar following a variety of stressors, including conditioned footshock, training with one footshock in passive avoidance behavior, performance of passive avoidance behavior, and even following exposure to an apparatus in which mice have been shocked previously. Injection of mice with Newcastle disease virus increases plasma corticosterone, and DOPAC and MHPG in the hypothalamus and brain stem, but not the prefrontal cortex. Thus a virus infection can be considered a stressor. Furthermore, intracerebroventricular (ICV) injection of corticotropin-releasing factor (CRF) produces stresslike increases in DOPAC and MHPG concentrations, suggesting that the release of CRF in the brain during stress may mediate the changes in catecholamine metabolism.