Repeated administration of MDMA down-regulates preprocholecystokinin mRNA expression but not tyrosine hydroxylase mRNA expression in neurones of the rat substantia nigra.
G Wotherspoon, D Savery, J V Priestley, M Rattray
Brain research. Molecular brain research August 1994 DOI: 10.1016/0169-328x(94)90275-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Dose | 10 mg/kg i.p., twice daily for 4 days |
| Duration | 4-day dosing; assessments at 24 hours and 2 weeks after the last dose |
| Measures | in situ hybridisation histochemistry, computerised image analysis of silver grain density |
| Topics | MDMA |
| Key findings | Repeated MDMA administration reduced CCK mRNA in the substantia nigra pars compacta at 24 hours and two weeks after the last dose, with no change in tyrosine hydroxylase mRNA. The authors argue this indicates MDMA can alter dopamine neurons and suggests the tyrosine hydroxylase and CCK genes are regulated independently despite being co-expressed. |
Abstract
The effect of repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) on the expression of tyrosine 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 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 results show that MDMA can produce changes in dopamine neurones. Furthermore, since tyrosine hydroxylase and cholecystokinin are co-expressed in substantia nigra pars compacta, these results suggest that the expression of the tyrosine hydroxylase and CCK genes are regulated independently.