Comparison of effects of hypotension and handling stress on the release of noradrenaline and dopamine in the locus coeruleus and medial prefrontal cortex of the rat

Abstract

The effects of two different types of stress (hypotension and handling) on the release of dopamine, noradrenaline and DOPAC in the locus coeruleus (LC) and medial prefrontal cortex (mPFC) was studied by means of the dual-probe microdialysis technique. One probe was implanted in the vicinity of the LC and a second probe was implanted in the mPFC. Both probes were used to record simultaneously noradrenaline, dopamine and DOPAC. Samples from the LC were collected in the presence of nomifensine, which was added to the perfusion fluid in a concentration of 50 microM. Hypotension (20 min) induced by intravenous administration of nitroprusside stimulated the release of noradrenaline in the LC and mPFC to about 190% and 150%, of control values, respectively. Hypotension also strongly stimulated the release of dopamine in the mPFC (to 320% of control) and DOPAC in the LC (to 270% of control). The effect of hypotension on extracellular dopamine, noradrenaline and DOPAC was decreased by halothane anaesthesia, and was blocked by chloral hydrate anaesthesia. Handling stress (10 min) stimulated the release of noradrenaline in the LC and mPFC to 180% and 160% of control values, respectively. Handling stimulated the release of dopamine in the mPFC to about 160% of control. The effect of hypotension or handling stress was further evaluated in animals in which the LC was lesioned by an infusion of 6-OH-dopamine. Lesioning of the noradrenergic LC neurons did not the prevent the hypotension-related stimulation of dopamine release, but shortened the time course of the effect dramatically. Lesioning of the noradrenergic neurons had no effect on the stimulatory effect of handling on the release of dopamine in the mPFC. This study shows that mesocortical dopamine neurons, in contrast to noradrenaline neurons, respond much stronger to hemodynamic stress than to an emotional stress. During certain conditions like hypotension stress, but not during handling stress, the LC activity is able to modulate the release of dopamine from mesocortical neurons.

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

“…Rather, endogenous 5-HT, released phasically, appears to activate cortical 5-HT2A receptors to subsequently stimulate DA release. Acute stress increases the release of cortical 5-HT (Figure 3; Kawahara et al, 1993) and DA (eg Abercrombie et al, 1989;Kawahara et al, 1999). The current findings demonstrate that blockade of cortical 5-HT2A receptors attenuates mild stress-induced DA release: this is the first evidence that cortical 5-HT2A antagonism blocks physiologically induced DA efflux in the mPFC.…”

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

“…The mPFC DA system is particularly sensitive to stress. This has been demonstrated by numerous microdialysis studies in which extracellular DA levels increased in the mPFC during exposure to diverse stressors (Davis et al, 1994;Finlay et al, 1995;Kawahara et al, 1999;Sorg and Kalivas, 1993;Sullivan and Gratton, 1998;Yoshioka et al, 1996).…”

“…DA efflux in the mPFC is increased during exposure to a wide variety of stressors including footshock (Sorg and Kalivas, 1993;Yoshioka et al, 1996), tail pinch (Finlay et al, 1995), cat odor (Sullivan and Gratton, 1998), and novelty (Davis et al, 1994). Even very mild stressors such as handling (Kawahara et al, 1999) can induce activation of mPFC DA. DA in the mPFC has previously been shown to be sensitive to stressor controllability in an ex vivo preparation (Carlson et al, 1993).…”

Acute Handling Stress Modulates Methylphenidate-induced Catecholamine Overflow in the Medial Prefrontal Cortex

“…The influential role of the NET in regulating DA overflow in the mPFC is further supported by a study resulting in significant DA increase after infusion of selective NET blocker desipramine (Gresch et al 1995). Interestingly, several studies suggest that changes in DA release during and following stress are not affected by andrenolectomy (Imperato et al 1991), or by 6-OH-DA lesions of the LC (Kawahara et al 1999).…”