The effects of dopamine and D2 receptor antagonists on pituitary hormone secretion are intact in mice lacking dopamine D2L receptor.

The dopamine D2 receptor (D2) is involved in the regulation of pituitary hormone secretion. Two isoforms of the D2 receptor, termed D2L and D2S, have been identified. We previously generated D2L knockout mice (D2L-/-), which still express D2S. The present study examined the role of D2S and D2L in spontaneous and drug-induced pituitary hormone secretion. We found that D2L-/- mice had normal serum levels of prolactin and growth hormone. In addition, the antipsychotic drugs haloperidol and clozapine induced a similar dose-dependent increase in serum prolactin in both D2L-/- and wild-type mice. These results suggest that D2S can substitute for the function of D2L in the regulation of pituitary hormone secretion, and that the function of D2S is not dependent on the formation of a receptor heterodimer with D2L.