Central κ-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: Behavioral and BDNF mRNA expression studies

Huina Zhang, Yong Gong Shi, James H. Woods, Stanley J. Watson, Mei Chuan Ko

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

κ-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 μg, 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 μ-, δ- and κ-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 κ-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 κ-opioid receptor mediates antidepressant-like effects of nor-BNI measured by both behavior and BDNF gene expression.

Original languageEnglish (US)
Pages (from-to)89-96
Number of pages8
JournalEuropean Journal of Pharmacology
Volume570
Issue number1-3
DOIs
StatePublished - Sep 10 2007
Externally publishedYes

Keywords

  • Depression
  • Hippocampus
  • In situ hybridization
  • Neurotrophin
  • κ-opioid receptor

ASJC Scopus subject areas

  • Pharmacology

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