Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: Behavioral and BDNF mRNA expression studies
Zhang H, Shi YG, Woods JH, Watson SJ, Ko MC.
Department of Pharmacology,
University of Michigan Medical School,
Ann Arbor, MI, USA;
Department of Biomedical Engineering,
College of Engineering,
University of Michigan,
Ann Arbor, MI, USA.
Eur J Pharmacol. 2007 Jun 9;


Kappa-opioid receptor antagonists such as nor-Binaltorphimine (nor-BNI) have been shown to produce antidepressant-like behavioral effects in animal models of depression. The aim of this study was to investigate further the duration of centrally administered nor-BNI-induced antidepressant-like actions measured by both behavior and brain-derived neurotrophic factor (BDNF) gene expression. In addition, antagonist studies were conducted to determine the role of opioid receptor subtypes and the time course of nor-BNI's pharmacological actions. Antidepressant-like behavioral effects were measured by decreased immobility in the rat forced swim test and BDNF mRNA expression was determined by in situ hybridization. Centrally administered nor-BNI (20 mug, i.c.v.) decreased immobility and increased BDNF mRNA expression in the hippocampus on day 1, not on days 3-14, post-administration. Systemic administration of selective mu-, delta- and kappa-opioid receptor antagonists did not block nor-BNI-induced antidepressant-like effects. In contrast, i.c.v. administration of nor-BNI 7 or 14 days earlier significantly blocked subsequent nor-BNI-induced decreased immobility and upregulation of BDNF mRNA expression. Although the duration of nor-BNI's antidepressant-like effects did not synchronize with that of its kappa-opioid receptor antagonist effects, this study is the first to show that centrally administered nor-BNI, like most clinically used antidepressants, can upregulate BDNF mRNA expression in the rat hippocampus. These findings further demonstrate that central kappa-opioid receptor mediates antidepressant-like effects of nor-BNI measured by both behavior and BDNF gene expression.
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Kappa opioid antagonists as antidepressants: norbinaltorphimine

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