REPEATED ADMINISTRATION OF MDMA DOWN-REGULATES PREPROCHOLECYSTOKININ MESSENGER-RNA EXPRESSION BUT NOT TYROSINE-HYDROXYLASE MESSENGER-RNA EXPRESSION IN NEURONS OF THE RAT SUBSTANTIA-NIGRA

The effect of repeated administration of 3,4-methylenedioxymethampheta mine (MDMA) on the expression of tyrosine hydroxylase and preprocholec ystokinin (CCK) messenger RNAs in substantia nigra was examined by in situ hybridisation histochemistry. Sections hybridised with S-35-label led oligonucleotides were subjected to computerised image analysis to determine the density of silver grains above positively labelled cells as an index of steady state mRNA levels. In the substantia nigra pars compacta, CCK mRNA levels were significantly reduced in drug-treated animals 24 h and at 2 weeks after the last dose of MDMA (10 mg/kg i.p. , twice daily for 4 days). In the same animals, MDMA caused no change in the level of tyrosine hydroxylase mRNA in this brain region. The re sults show that MDMA can produce changes in dopamine neurones. Further more, since tyrosine hydroxylase and cholecystokinin are co-expressed in substantia nigra pars compacta, these results suggest that the expr ession of the tyrosine hydroxylase and CCK genes are regulated indepen dently.