Repeated administration of MDMA down-regulates tion preprocholecystokinin mRNA expression but not tyrosine hydroxylase rone ' n mRNA expression in neurones of the rat substantia nigra

The effect of repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) on the expression of tyrosinc hydroxylase and preprocholecystokinin (CCK) messenger RNAs in substantia nigra was examined by in situ hybridisation histochemistry. Sections hybridised with 35S-labelled oligonucleotides were subjected to computerised image analysis to determine the densiw 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 results show that MDMA can produce changes in dopamine neurones. Furthermore, since tyrosine hydroxylase and cholecystokinin arc co-expressed in substantia nigra pars compaeta, these results suggest that the expression of the tyrosine hydroxylase and CCK genes are regulated independently.