ALPHA(1)-ADRENERGIC, D-1, AND D-2 RECEPTORS INTERACTIONS IN THE PREFRONTAL CORTEX - IMPLICATIONS FOR THE MODALITY OF ACTION OF DIFFERENT TYPES OF NEUROLEPTICS

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 c ells. In the present; study, it was first shown that systemic administ ration of either clozapine (a mixed antagonist of D-1, D-2, and alpha( 1)-adrenergic receptors) (3-5 mg/kg, i.v.), prazosin (an alpha(1)-adre nergic antagonist) (0.2 mg/kg, i.v.), or sulpiride (a D-2 antagonist) (30 mg/kg, i.v.), but not SCP-I 23390 (a D-1 antagonist) (0.2 mg/kg, i .v.), reversed this cortical inhibition. Second, it was found that fol lowing the systemic administration of prazosin, the VTA-induced cortic al inhibition reappeared when either SCH 23390 or sulpiride was applie d 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 b locks alpha(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 t hat the cortical inhibitions obtained following treatments with either ''prazosin plus sulpiride'' or ''prazosin plus SCH 23390'' were block ed by a superimposed administration of either SCH 23390 or sulpiride, respectively. These data indicate that complex interactions between co rtical D-2, D-1, and alpha(1)-adrenergic receptors are involved in the regulation of the activity of prefrontocortical cells innervated by t he VTA neurons. They confirm that the physiological stimulation of cor tical alpha(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 transmis sion. (C) 1998 Wiley-Liss, Inc.