DIFFERENTIAL-EFFECTS ON D-2 DOPAMINE-RECEPTOR AND PROLACTIN GENE-EXPRESSION BY HALOPERIDOL AND ARIPIPRAZOLE IN THE RAT PITUITARY

[H-3]Spiperone-binding assay to D-2 receptors and quantitative ribonuc lease protection assay for both isoforms (D-2L and D-2S receptor) of t he D-2 receptor mRNA and the prolactin mRNA were performed on pituitar ies from the control rat and from the rat injected orally daily with e ither haloperidol (2 mg/kg) or aripiprazole (24 mg/kg) for 21 days. Ha loperidol treatment increased the [H-3]spiperone-binding by 28%, the l evels of D-2L and D-2S receptor mRNA by 41% and 38%, respectively, and the level of prolactin mRNA by 26%. In contrast, the treatment with a ripiprazole, a newly developed atypical antipsychotic with reduced sid e effects, decreased the [H-3]spiperone-binding by 24% and the levels of D-2L and D-2S receptor mRNA by 23% and 23%, respectively, and did n ot have any effect on the level of prolactin mRNA. The same treatment with sulpiride (100 mg/kg) increased the levels of D-2L and D-2S recep tor mRNA by 59% and 62%, respectively, but treatment with clozapine (2 5 mg/kg) did not cause any effect. Neither treatment changed the ratio of the level of D-2S receptor mRNA to the level of D-2L receptor mRNA in the pituitary. These findings indicate that D-2 receptor densities in the pituitary are influenced differentially by the treatment with these antipsychotics, which could be induced at least pastry by the ch anges in the levels of mRNA without any effects on the splicing mechan isms and thus affect the plasticity of the prolactin mRNA expression. The inhibitory effects of chronic aripiprazole treatment on D-2 recept ors in the pituitary might underlie this drug's clinical property of r educed hyperprolactinemia side effect. (C) 1998 Elsevier Science B.V.