DIFFERENTIAL PLASTICITY OF THE DOPAMINERGIC-D2 RECEPTOR MESSENGER-RNA ISOFORMS UNDER HALOPERIDOL TREATMENT, AS EVIDENCED BY INSITU HYBRIDIZATION IN RAT ANTERIOR-PITUITARY

Quantitative in situ hybridization with S-35-radiolabelled oligonucleotidic probes complementary either to the common sequence of both isoforms (D2(415) and D2(444)) of the D2 receptor mRNA, or to the specific sequence of the long isoform (D2(444)), and also to prolactin mRNA, was performed on pituitaries from control male rats and from rats injected daily with haloperidol (5 mg/kg, i.m.) for 3 or 30 days. It was shown that the D2(444)-mRNA mRNA is expressed in both anterior and intermediate lobes. In the anterior lobe, haloperidol treatment did not modify the hybridization signal specific for the D2(444)-mRNA, whereas long term (30 days) - but not short term (3 days) - treatment significantly increased the hybridization signal for the common sequence (D2(415) + D2(444)) by about 20%, suggesting an increased expression of the short isoform (D2(415)). Prolactin mRNA content was increased by the third day of haloperidol treatment. This neuroleptic-induced alteration in the ratio of both D2 receptor isoforms suggests changes in mRNA splicing regulatory processes, which could represent an alternative way to modulate receptor sensitivity, through differential plasticity of each isoform's expression.