Regional differences in the regulation of dopamine and noradrenaline release in medial frontal cortex, nucleus accumbens and caudate-putamen: a microdialysis study in the rat.

Dopamine (DA) and noradrenaline (NA) extracellular levels have been measured by microdialysis in the medial frontal cortex (MFC), nucleus accumbens (NAc) and caudate-putamen (CP) under baseline conditions in awake and halothane-anaesthetized rats, and after application of three types of stimuli which are likely to activate the brainstem catecholaminergic systems: mild stressors (handling and tail pinch), rewarded behavior (eating palatable food without prior food deprivation) and electrical stimulation of the lateral habenular nucleus. Changes were studied with and without uptake blockade (10 microM nomifensine in the perfusion fluid). The influence of calcium concentration (1.2 or 2.3 mM in the perfusion fluid) on DA and NA overflow was tested in some cases. Handling and tail pinch stimulated both DA and NA overflow in MFC, and enhanced NA overflow in NAc. By contrast, these mildly stressful stimuli had only marginal effects on DA overflow in NAc and no effects on either DA or NA overflow in CP. Eating behavior was accompanied by increased DA and NA overflow in MFC but had no effect in NAc. These regional differences were similar also when the manipulations were applied under uptake blockade, which indicates that the more pronounced changes seen in MFC did not simply reflect a more sparse innervation (i.e. lower density of uptake sites) in the MFC compared to the more densely innervated NAc and CP areas. Stimulation of the lateral habenula induced a 2-3-fold increase in NA overflow in both MFC, NAc and CP but had no consistent effect on DA overflow in any region. The effect on NA release was abolished by a transection of the ipsilateral fasciculus retroflexus (which carries the efferent output of the lateral habenula). The results show that the forebrain DA and NA projections to cortical and striatal targets are differentially regulated during ongoing behavior, that the mesocortical and mesostriatal DA systems respond quite differently to stressful and rewarding stimuli; and that the NA projection to MFC (like the dopaminergic one) is more responsive to stressful and rewarding stimuli than the ones innervating the striatum (NAc and CP). The results support the view that environmental stimuli evoking emotional arousal (whether aversive or non-aversive) are accompanied by increased DA and NA release above all in the MFC and only to a minor extent in limbic and striatal areas.