The activation of rat mesocortical dopaminergic (DA) neurons evoked by the electrical stimulation of the ventral tegmental area (VTA) induces a marked inhibition of the spontaneous activity of prefrontocortical cells. In the present study, it was first shown that systemic administration of either clozapine (a mixed antagonist of D 1 , D 2 , and ␣ 1 -adrenergic receptors) (3-5 mg/kg, i.v.), prazosin (an ␣ 1 -adrenergic antagonist) (0.2 mg/kg, i.v.), or sulpiride (a D 2 antagonist) (30 mg/kg, i.v.), but not SCH 23390 (a D 1 antagonist) (0.2 mg/kg, i.v.), reversed this cortical inhibition. Second, it was found that following the systemic administration of prazosin, the VTA-induced cortical inhibition reappeared when either SCH 23390 or sulpiride was applied by iontophoresis into the prefrontal cortex. Third, it was seen that, whereas haloperidol (0.2 mg/kg, i.v.), a D 2 antagonist which also blocks ␣ 1 -adrenergic receptors, failed to reverse the VTA-induced inhibition, the systemic administration of haloperidol plus SCH 23390 (0.2 mg/kg, i.v.) blocked this inhibition. Finally, it was verified that the cortical inhibitions obtained following treatments with either ''prazosin plus sulpiride'' or ''prazosin plus SCH 23390'' were blocked by a superimposed administration of either SCH 23390 or sulpiride, respectively. These data indicate that complex interactions between cortical D 2 , D 1 , and ␣ 1 -adrenergic receptors are involved in the regulation of the activity of prefrontocortical cells innervated by the VTA neurons. They confirm that the physiological stimulation of cortical ␣ 1 -adrenergic receptors hampers the functional activity of cortical D 1 receptors and suggest that the stimulations of cortical D 1 and D 2 receptors exert mutual inhibition on each other's transmission.