EVIDENCE THAT EXTRACELLULAR CONCENTRATIONS OF DOPAMINE ARE REGULATED BY NORADRENERGIC NEURONS IN THE FRONTAL-CORTEX OF RATS

Experiments were performed to confirm that noradrenergic terminals reg ulate extracellular concentrations of dopamine (DA) in the frontal cor tex of rats. The effects of 20 mg/kg henyl)methoxy]-ethyl]-4-(3-phenyl propyl)piperazine (GBR 12909), a selective inhibitor of DA uptake, and 2.5 mg/kg desipramine (DMI) on the extracellular concentrations of DA in the frontal cortex and striatum were studied in rats given 6-hydro xydopamine (6 mu g/mu l) bilaterally into the locus coeruleus to destr oy noradrenergic terminals. GBR 12909 increased dialysate DA similarly in the striatum of vehicle and 6-hydroxydopamine-treated rats, wherea s in the frontal cortex it raised DA concentrations only in lesioned a nimals. DMI raised extracellular DA concentrations in the frontal cort ex but not in the striatum of controls. The effect of DMI on cortical DA was abolished by the 6-hydroxydopamine lesion. GBR 12909, at a subc utaneous dose of 20 mg/kg, further increased cortical dialysate DA in rats given DMI intraperitoneally at 20 mg/kg or through the probe at 1 0(-5) mol/L. The data support the hypothesis of an important regulatio n of the extracellular concentrations of DA in the frontal cortex by n oradrenergic terminals.