期刊
PLOS ONE
卷 7, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0050264
关键词
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资金
- Ministerio de Ciencia e Imnovacion, Spain [SAF/FEDER 2009-07178, SAF/FEDER 2010-17907]
- Red de Trastornos Adictivos, Spain [RD06/0001/1006, RD06/0001/1001]
- Fundacion Seneca, Agencia Regional de Ciencia y Tecnologia Region de Murcia, Spain [15405/PI10]
- Ministerio de Ciencia e Innovacion [AP2009-2379]
Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor Delta FosB, particularly in brain areas associated with reward and stress. The persistent effects of Delta FosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e. g., glucocorticoids, GC) may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/Delta FosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/Delta FosB was measured in control (sham-operated) and adrenalectomized (ADX) rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/Delta FosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell) (NAc), bed nucleus of the stria terminalis (BNST), central amygdala (CeA), hypothalamic paraventricular nucleus (PVN) and nucleus of the solitary tract noradrenergic cell group (NTS-A(2)). Adrenalectomy attenuated the increased production of FosB/Delta FosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/Delta FosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2) TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/Delta FosB) to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.
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