Alpha1-adrenergic, D1, and D2 receptors interactions in the prefrontal cortex: implications for the modality of action of different types of neuroleptics

Synapse. 1998 Dec;30(4):362-70. doi: 10.1002/(SICI)1098-2396(199812)30:4<362::AID-SYN3>3.0.CO;2-W.


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 D1, D2, and alpha1-adrenergic receptors) (3-5 mg/kg, i.v.), prazosin (an alpha1-adrenergic antagonist) (0.2 mg/kg, i.v.), or sulpiride (a D2 antagonist) (30 mg/kg, i.v.), but not SCH 23390 (a D1 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 D2 antagonist which also blocks alpha1-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 D2, D1, and alpha1-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 alpha1-adrenergic receptors hampers the functional activity of cortical D1 receptors and suggest that the stimulations of cortical D1 and D2 receptors exert mutual inhibition on each other's transmission.

MeSH terms

  • Animals
  • Antipsychotic Agents / therapeutic use
  • Benzazepines / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology
  • Clozapine / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Electric Stimulation
  • Electrophysiology
  • Haloperidol / pharmacology
  • Injections, Intravenous
  • Iontophoresis
  • Neural Inhibition / drug effects
  • Prazosin / pharmacology
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha / physiology*
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D2 / physiology*
  • Sulpiride / pharmacology


  • Antipsychotic Agents
  • Benzazepines
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Sulpiride
  • Clozapine
  • Haloperidol
  • Prazosin