| Autor: |
Boundy VA; Laboratory of Molecular Psychiatry, Departments of Psychiatry and Neurobiology, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut 06508, USA., Gold SJ, Messer CJ, Chen J, Son JH, Joh TH, Nestler EJ |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 1998 Dec 01; Vol. 18 (23), pp. 9989-95. |
| Abstrakt: |
Levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, are known to be upregulated in specific brain regions by chronic administration of drugs of abuse. Chronic morphine administration increases TH levels in the locus coeruleus and ventral tegmental area, whereas chronic cocaine administration increases TH levels in the ventral tegmental area only. While such upregulation of TH has been related to behavioral effects of the drugs, the mechanism underlying these adaptations has remained controversial. To study the possibility that upregulation of TH occurs at the transcriptional level, we investigated the effect of chronic morphine or cocaine treatment on the activity of the TH gene promoter (9.0 kb), coupled to the LacZ reporter gene, in transgenic mice. These TH9.0-LacZ mice have been shown to exhibit correct tissue-specific expression and regulation of the reporter gene. We show here that chronic (but not acute) exposure of the TH9.0-LacZ mice to morphine increases the expression of beta-galactosidase (which is encoded by the LacZ gene) in the locus coeruleus by twofold compared with sham-treated mice. In contrast, beta-galactosidase expression in the ventral tegmental area was decreased 20-25% by chronic morphine and unaffected by chronic cocaine administration. Similar results were obtained after analysis of TH mRNA levels in these brain regions by in situ hybridization. These results suggest that chronic morphine upregulates TH expression via transcriptional mechanisms in the locus coeruleus but by post-transcriptional mechanisms in the ventral tegmental area. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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