title: Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.
abstract: Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB 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/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB 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/ΔFosB 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/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB 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/ΔFosB) to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.
authors.affiliation: Group of Cellular and Molecular Pharmacology, Department of Pharmacology, University School of Medicine, Murcia, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Pérez
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Laorden
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Milanés
authors.forename: Cristina
authors.initials: C
authors.lastname: Núñez
mesh_terms: D000315:Adrenalectomy; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000209:etiology / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D004745:Enkephalins; C483820:Fosb protein, rat; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine; C033660:preproenkephalin; D003345:Corticosterone