Induction of FosB/ΔFosB in the brain stress system-related structures during morphine dependence and withdrawal

Cristina Núñez, Fátima Martín, Anna Földes, M. Luisa Laorden, Krisztina J. Kovács, M. Victoria Milanés

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The transcription factor ΔFosB is induced in the nucleus accumbens (NAc) by drugs of abuse. This study was designed to evaluate the possible modifications in FosB/ΔFosB expression in both hypothalamic and extrahypothalamic brain stress system during morphine dependence and withdrawal. Rats were made dependent on morphine and, on day 8, were injected with saline or naloxone. Using immunohistochemistry and western blot, the expression of FosB/ΔFosB, tyrosine hydroxylase (TH), corticotropin-releasing factor (CRF) and pro-dynorphin (DYN) was measured in different nuclei from the brain stress system in morphine-dependent rats and after morphine withdrawal. Additionally, we studied the expression of FosB/ΔFosB in CRF-, TH- and DYN-positive neurons. FosB/ΔFosB was induced after chronic morphine administration in the parvocellular part of the hypothalamic paraventricular nucleus (PVN), NAc-shell, bed nucleus of the stria terminalis, central amygdala and A2 noradrenergic part of the nucleus tractus solitarius (NTS-A2). Morphine dependence and withdrawal evoked an increase in FosB/ΔFosB-TH and FosB/ΔFosB-CRF double labelling in NTS-A 2 and PVN, respectively, besides an increase in TH levels in NTS-A2 and CRF expression in PVN. These data indicate that neuroadaptation to addictive substances, observed as accumulation of FosB/ΔFosB, is not limited to the reward circuits but may also manifest in other brain regions, such as the brain stress system, which have been proposed to be directly related to addiction.

Original languageEnglish
Pages (from-to)475-487
Number of pages13
JournalJournal of neurochemistry
Issue number2
Publication statusPublished - Jul 1 2010



  • FosB/ΔFosB
  • brain stress system
  • corticotropin-releasing factor
  • dynorphin
  • morphine
  • tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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