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.