We examined the effects of an interruption of dopamine neurotransmission, by either dopamine receptor blockade or degeneration of dopamine neurons by 6‐hydroxydopamine, on the levels of D₂ receptor mRNAs. In addition, we evaluated by the polymerase chain reaction (PCR) the relative abundance of the two D₂ receptor isoform mRNAs generated by alternative splicing. Daily injections of 4 mg/kg of haloperidol to rats elicited in striatum a rapid and progressive increase in D₂ receptor mRNA levels, which reached 70% after a 15‐day treatment. By contrast, there was no apparent change in D₂ receptor mRNA levels in cerebral cortex and pons‐medulla, in spite of an increased density of D₂ receptor in the former tissue. Using the PCR with primers flanking the alternative exon, we observed that the relative proportion of the shorter receptor isoform (D_2s) mRNA was slightly but significantly enhanced in cerebral cortex (17%) and pons‐medulla (18%) after a 15‐day haloperidol treatment. Unilateral degeneration of dopamine neurons induced by local injection of 6‐hydroxydopamine resulted in a marked decrease in levels of total D₂ receptor mRNAs in substantia nigra (—79%) and ventral tegmental (—63%) area, two cell body areas. In the substantia nigra, the longer isoform (D_2l) mRNA was significantly more decreased in content than the D_2s isoform mRNA, so that there was a large enhancement in the relative abundance of the latter (81%). In contrast, the lesion did not result in any significant change in levels of total D₂ receptor mRNAs in striatum, but the relative proportion of D_2s receptor mRNA tended to decrease—although nonsignificantly—as a result of a tendency of the D_2l receptor mRNA abundance to rise. The present study establishes that two distinct processes of D₂ receptor gene expression accompany and may contribute to the hypersensitivity known to develop at D₂ receptors following either their chronic blockade by neuroleptics or dopamine denervation.

Publications with shared reference:

0 publications found