THE EXPRESSION OF PROENKEPHALIN AND PRODYNORPHIN GENES AND THE INDUCTION OF C-FOS GENE BY DOPAMINERGIC DRUGS ARE NOT ALTERED IN THE STRIATUM OF MPTP-TREATED MICE

The expression of proenkephalin (PENK), prodynorphin (PDYN) and c-fos genes was studied in the striatum of C57B1/6 mice treated with 1-methy l-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP), which are used as a rod ent model of Parkinson's disease (PD). Two weeks after systemic admini stration of MPTP (2 x 40 mg/kg, s.c. 18 h apart), the lesion of the su bstantia nigra (SN) could be visualised by loss of the nigral tyrosine hydroxylase (TH) mRNA hybridization signal and by a 91% decrease in s triatal dopamine levels. The levels of PENK and PDYN mRNAs were not si gnificantly changed in the striatum of the lesioned mice, as compared to non-treated controls. The induction of the immediate early gene c-f os by the dopamine D-2 receptor antagonist haloperidol was not altered , while the selective D, receptor agonist SKF 38393 failed to induce c -fos in the striatum of MPTP-treated mice. These results are in contra st to the data concerning rats with the 6-hydroxydopamine (6-OHDA) les ion of the SN, which serve as another rodent model of PD. In the stria ta of 6-OHDA-lesioned rats, PENK gene is upregulated, PDYN gene is dow n-regulated and the induction of c-fos gene by D-2 receptor antagonist s is abolished, whereas selective D-1 receptor agonists induce c-fos g ene, which does not occur in non-lesioned rats. We presume that the la ck of influence of the MPTP lesion in mice on the striatal gene expres sion was mainly caused by insufficient dopamine depletion in the stria tum, which could not be increased in this model. The importance of the changes observed in 6-OHDA-lesioned rats has been discussed in the co ntext of the mouse and primate MPTP models of PD.