Premium
Effects of Dopaminergic Transmission Interruption on the D 2 Receptor Isoforms in Various Cerebral Tissues
Author(s) -
Martres M. P.,
Sokoloff P.,
Giros B.,
Schwartz J. C.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09770.x
Subject(s) - substantia nigra , medicine , endocrinology , dopamine , striatum , ventral tegmental area , pons , biology , dopamine receptor , dopaminergic , receptor , cerebral cortex
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 D 2 receptor mRNAs. In addition, we evaluated by the polymerase chain reaction (PCR) the relative abundance of the two D 2 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 D 2 receptor mRNA levels, which reached 70% after a 15‐day treatment. By contrast, there was no apparent change in D 2 receptor mRNA levels in cerebral cortex and pons‐medulla, in spite of an increased density of D 2 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 2 s ) 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 D 2 receptor mRNAs in substantia nigra (—79%) and ventral tegmental (—63%) area, two cell body areas. In the substantia nigra, the longer isoform (D 2 l ) mRNA was significantly more decreased in content than the D 2 s 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 D 2 receptor mRNAs in striatum, but the relative proportion of D 2 s receptor mRNA tended to decrease—although nonsignificantly—as a result of a tendency of the D 2 l receptor mRNA abundance to rise. The present study establishes that two distinct processes of D 2 receptor gene expression accompany and may contribute to the hypersensitivity known to develop at D 2 receptors following either their chronic blockade by neuroleptics or dopamine denervation.