Elevation of plasma prolactin concentrations by intravenous SCH 23390 and SKF 38393 in conscious rats.

The effect of the selective dopamine-1 (D-1) antagonist, SCH 23390 and the selective D-1 agonist, SKF 38393 on plasma prolactin levels was investigated in conscious, freely moving male rats. Plasma prolactin was markedly increased by the intravenous injection of either SCH 23390 or SKF 38393 in a dose-related fashion. The maximal prolactin response was observed 15 min after drug injection. The d-isomer of SKF 38393 was significantly more potent than the l-isomer. In urethane-anesthetized rats, the two drugs produced similar effects on prolactin as those in the conscious animal preparation. Both SCH 23390 and SKF 38393 potentiated the sulpiride-induced prolactin elevation. These observations suggest that pharmacologic stimulation, or blockade of D-1 receptors in the living animal, can mimic the action of a D2 antagonist at the anterior pituitary lactotroph. We have speculated on the possible mechanisms in pituitary and higher in the central nervous system which might be responsible for the prolactin changes caused by either SCH 23390 or SKF 38393.