CHANGES OF D-1 AND D-2 DOPAMINE-RECEPTOR MESSENGER-RNA IN THE BRAINS OF MONKEYS LESIONED WITH 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE - CORRECTION WITH CHRONIC ADMINISTRATION OF L-3,4-DIHYDROXYPHENYLALANINE

The effect of L-3,4-dihydroxyphenylalanine (L-DOPA) on dopamine recept or gene expression in the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine (MPTP)-lesioned monkeys was investigated using in situ hybri dization histochemistry with measures of changes in relative absorbanc e. In MPTP-lesioned monkeys, a decrease of D-1 dopamine receptor mRNAs was observed in the rostral part of the caudate and putamen compared with control animals (-20% and -17%, respectively, in the lateral axis ). Chronic treatment of MPTP-lesioned monkeys with L-DOPA returned the ir D-1 receptor mRNA values to near those of control monkeys in the ca udate and putamen (92% and 91% of control values, respectively). No le sion or drug-induced changes of D-1 receptor mRNAs were observed in th e more caudal parts of the striatum. A decrease of D-1 receptor mRNAs was observed in the olfactory tubercule (-22%) in MPTP-lesioned monkey s compared with control animals but no change was seen in the nucleus accumbens. D-1 receptor mRNAs in the anterior cerebral cortex were dec reased in MPTP-lesioned monkeys (-19% compared with control animals). D-1 receptor mRNAs in olfactory tubercle and in cerebral cortex of L-D OPA-treated MPTP-lesioned monkeys were not significantly different fro m control animals. For D-2 receptor mRNAs, we observed an increase in the caudal part of the caudate and putamen (+24% and +23%, respectivel y, in MPTP-lesioned monkeys compared with control animals). Chronic L- DOPA treatment corrected this elevation to control values. No variatio n of D-2 receptor mRNAs was seen in the more rostral parts of the stri atum and in the nucleus accumbens in MPTP-lesioned monkeys as well as in MPTP-lesioned monkeys treated chronically with L-DOPA. Our results show for the first time that L-DOPA can influence gene expression of D -1 and D-2 receptors in MPTP-lesioned monkeys and correct the lesion-i nduced increase in the expression of D-2 receptors, whereas the correc tion of the D-1 receptor expression decrease is only partial. Furtherm ore, the changes in gene expression of D-1 and D-2 receptors in MPTP-l esioned monkeys are regional: they are restricted to the anterior stri atum for the D-1 receptors and the posterior striatum for the D-2 rece ptors.