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Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: behavioral and BDNF mRNA expression studies.
Eur J Pharmacol. 2007 Sep 10; 570(1-3):89-96.EJ

Abstract

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 microg, 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.

Authors+Show Affiliations

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17601558

Citation

Zhang, Huina, et al. "Central Kappa-opioid Receptor-mediated Antidepressant-like Effects of nor-Binaltorphimine: Behavioral and BDNF mRNA Expression Studies." European Journal of Pharmacology, vol. 570, no. 1-3, 2007, pp. 89-96.
Zhang H, Shi YG, Woods JH, et al. Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: behavioral and BDNF mRNA expression studies. Eur J Pharmacol. 2007;570(1-3):89-96.
Zhang, H., Shi, Y. G., Woods, J. H., Watson, S. J., & Ko, M. C. (2007). Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: behavioral and BDNF mRNA expression studies. European Journal of Pharmacology, 570(1-3), 89-96.
Zhang H, et al. Central Kappa-opioid Receptor-mediated Antidepressant-like Effects of nor-Binaltorphimine: Behavioral and BDNF mRNA Expression Studies. Eur J Pharmacol. 2007 Sep 10;570(1-3):89-96. PubMed PMID: 17601558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: behavioral and BDNF mRNA expression studies. AU - Zhang,Huina, AU - Shi,Yong-Gong, AU - Woods,James H, AU - Watson,Stanley J, AU - Ko,Mei-Chuan, Y1 - 2007/06/09/ PY - 2007/01/03/received PY - 2007/05/17/revised PY - 2007/05/22/accepted PY - 2007/7/3/pubmed PY - 2007/12/6/medline PY - 2007/7/3/entrez SP - 89 EP - 96 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 570 IS - 1-3 N2 - 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 microg, 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17601558/Central_kappa_opioid_receptor_mediated_antidepressant_like_effects_of_nor_Binaltorphimine:_behavioral_and_BDNF_mRNA_expression_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00651-6 DB - PRIME DP - Unbound Medicine ER -