Neurochemical interaction between dopaminergic and noradrenergic neurons in the medial prefrontal cortex

Growing evidence indicates that there is an interaction between the transmission of dopamine (DA) and norepinephrine (NE) in the noradrenergic and dopaminergic projections that converge in the medial prefrontal cortex (mPFC). The effects of the noradrenergic α1 and α2 receptors and the NE transporters on the DA outflow and those of the dopaminergic D1 and D2 receptors on NE release in the mPFC were investigated. Local infusions of NE (90, 150, and 300 nM) into the mPFC increased the extracellular release of DA in anesthetized rats. The α1 receptor antagonist (10 μM prazosin), but not the α2 receptor antagonist (100 μM piperoxan), blocked the NE-induced increase of DA in the mPFC. In addition, local infusion of α1 receptor agonist (10 μM phenylephrine) enhanced DA release in the mPFC. Local application of DA in different concentrations into the mPFC increased extracellular NE levels. Intra-mPFC infusion of a D1 receptor antagonist (10 nM SCH23390), inhibited the DA-induced increase of NE; this did not happen with a D2 receptor antagonist (1 nM eticlopride). Local administration of a selective NE uptake inhibitor (1 μM desmethylimipramine) into the mPFC increased the outflows of both DA and NE in the mPFC. However, co-infusion of DMI and prazosin blunted, but did not totally abolish, the DMI-increase in the extracellular levels of DA and NE. These results suggest that in the mPFC, 1) extracellular NE could enhance DA release by activating the α1 receptors; and 2) extracellular DA increased the extracellular levels of NE by activating the D1 receptors. Synapse 53:44–52, 2004. © 2004 Wiley-Liss, Inc.