The Medial Prefrontal Cortex Determines the Accumbens Dopamine Response to Stress through the Opposing Influences of Norepinephrine and Dopamine

Abstract

Although the medial prefrontal cortex (mpFC) appears to constrain stress responses, indirect evidences suggest that it might determine the stress response of the mesoaccumbens dopamine (DA) system. To test this hypothesis, we first evaluated the dynamics of norepinephrine (NE) and DA release in the mpFC and of DA release in the nucleus accumbens (NAc) of acutely stressed rats. Then, we tested the effects of selective depletion of NE or DA in the mpFC (by local 6-hydroxydopamine infusion following desipramine or 1-[2[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine(GBR 12909) on stress-induced changes in mesoaccumbens DA release. Rats experiencing restraint stress for 240 min showed an initial, short-lived increase of NE outflow in the mpFC and of DA in the NAc. These responses were followed by a sustained increase of DA in the mpFC and by a decrease to below resting levels of DA in the NAc. Moreover, selective prefrontal NE depletion eliminated the increase of NE in the mpFC and of DA in the NAc, and selective depletion of mesocortical DA eliminated the enhancement of mpFC DA as well as the inhibition of mesoaccumbens DA, without affecting basal catecholamines outflow. These results demonstrate that the opposing influences of mpFC NE and DA determine mesoaccumbens DA response to stress and suggest that alterations of this mechanism may be responsible for some major psychopathological outcomes of stress.

Original article Sertraline and curcumin prevent stress-induced morphological changes of dendrites and neurons in the medial prefrontal cortex of rats

“…Nevertheless, previous studies have shown that repeat- ed stress reduced dopamine [22,27], noradrenalin [14], and serotonin in the mPFC [20]. Experimental findings also emphasize that serotonin changes spine density and dendrite length in the mPFC by acting on 5-HT receptors [21].…”

Stress improves task processing efficiency in dual-tasks

“…Punishments have been shown to exert their effects via the dopamine D2 receptor system [32] in the nucleus accumbens [e.g., 33]. Similarly, stress has been shown to predominantly affect the dopamine D2 receptor system in the nucleus accumbens [17,18], which is at least partly mediated by activation of glucocorticoid receptors by cortisol [18]. It is therefore possible that the modulatory effects of stress on dual-task processing efficiency may be mediated via the effect of glucocorticoids on dopamine D2 receptors.…”

“…However, psychological stress has been suggested to affect catecholaminergic signalling [16] and dopamine D2 receptor related neural transmission in particular [e.g., 17,18]. Response control processes, as examined using the PRP, have been shown to depend on dopaminergic neural transmission and fronto-striatal networks [e.g., [19][20][21].…”

“…Punishments have been shown to be mediated via the dopamine D2 receptor system and hence a receptor system that plays an important role in the mediation of stress effects on cognitive functions [16][17][18]. Against this background it is therefore more likely that stress increases dual-tasking performance, i.e., leads to faster reaction times on task two in short SOAs.…”

Corticotropin releasing factor and neuroplasticity in cocaine addiction

“…In the PFC, dopaminergic activity is increased in response to different kinds of stressors in animal models (Abercrombie et al 1989;Deutch et al 1985;Imperato et al 1989;Matuszewich et al 2002;Pascucci et al 2007). However, the stress-induced increase in DA transmission is transient and rapidly returns to baseline levels (Abercrombie et al 1989;Gresch et al 1994).…”