Absence of [3H]SCH 23390 specific binding sites in anterior pituitary: dissociation from effects on prolactin...

We extended a previous study that had shown the selective D1 receptor antagonist SCH 23390, at relatively high doses, to stimulate prolactin (PRL) secretion in the rat and weakly inhibit [3H]spiperone binding to striatum and anterior pituitary (AP) membranes. No specific [3H]SCH 23390 binding sites, up to the micromolar range, were detected in rat AP while specific, saturable [3H]SCH 23390 binding sites (low nanomolar range) were observed in the striatum. In vivo SCH 23390 (1 mg/kg s.c.) induced higher plasma PRL levels, not reversible by the D1 agonist SKF 38393. Similarly the postsynaptic serotonin (5-HT) antagonists metergoline and cyproheptadine did not influence the SCH 23390 effect on PRL. SCH 23390 was also unable to antagonize the decrease of PRL secretion induced by the selective D2 agonist LY 171555. However this latter compound prevented SCH 23390 as well as sulpiride from increasing the PRL concentrations above the control values. These data rule out the possibility that D1 or 5-HT receptors mediate the stimulation of PRL release by SCH 23390. This effect is more likely to be due to a weak indirect interaction with AP-D2 receptors, as indicated by the non-competitive inhibition of [3H]spiperone binding to AP exerted by SCH 23390. Alternatively, non-specific mechanisms triggered by the multiple behavioral changes elicited by such high doses of SCH 23390 may be involved.