Blockade of D-1 dopamine receptors by SCH 23390 prevents EEG and behavioral activation induced by L-dopa

Administration of L-DOPA, a precursor of dopamine, induced EEG activation, arousal and signs of behavioral excitation in the rabbit. The effects were fully prevented by pretreatment with minute doses (0.01 mg/kg i.v.) of the selective D-1 antagonist SCH 23390. Conversely, its S-enantiomer SCH 23388, which has weak actions on D-1 receptors, displayed relatively low inhibition of L-DOPA effects. (-)-Sulpiride (12.5 mg/kg), a selective D-2 antagonist, and haloperidol (0.1-0.3 mg/kg), a neuroleptic that interacts preferentially with D-2 receptors, both inhibited behavioral effects but failed to block EEG activation. The data indicate that D-1 receptors play an essential role in mediating EEG activation induced by L-DOPA.