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Endogenous opioids upregulate brain‐derived neurotrophic factor mRNA through δ‐ and µ‐opioid receptors independent of antidepressant‐like effects
Author(s) -
Zhang Huina,
Torregrossa Mary M.,
Jutkiewicz Emily M.,
Shi YongGong,
Rice Kenner C.,
Woods James H.,
Watson Stanley J.,
Holden Ko M. C.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04621.x
Subject(s) - naltrindole , endogenous opioid , endocrinology , brain derived neurotrophic factor , medicine , agonist , opioid receptor , opioid , damgo , opioid peptide , neurotrophic factors , chemistry , pharmacology , tropomyosin receptor kinase b , enkephalin , antagonist , receptor
Systemic administration of δ‐opioid receptor (DOR) agonists decreases immobility in the forced swim test (FST) and increases brain‐derived neurotrophic factor (BDNF) mRNA expression in rats, indicating that DOR agonists may have antidepressant‐like effects. The aim of this study was to investigate the effects of central administration of endogenous opioid peptides on behavior in the FST and on brain BDNF mRNA expression in rats. Effects of endogenous opioids were compared with those produced by intracerebroventricular administration of a selective non‐peptidic DOR agonist (+)BW373U86. Antidepressant‐like effects were measured by decreased immobility in the FST. BDNF mRNA expression was determined by in situ hybridization. Centrally administered (+)BW373U86 decreased immobility and increased BDNF mRNA expression in the frontal cortex through a DOR‐mediated mechanism, because these effects were blocked by the DOR antagonist naltrindole, but not by the µ‐opioid receptor (MOR) antagonist naltrexone (NTX) or the κ‐opioid receptor antagonist nor‐binaltorphimine. Of all the endogenous opioids tested, only leu‐ and met‐enkephalin produced behavioral effects like those of (+)BW373U86 in the FST. Unlike (+)BW373U86, the enkephalins upregulated BDNF mRNA expression in the hippocampus through DOR‐ and MOR‐mediated mechanisms. β‐Endorphin, endomorphin‐1 and endomorphin‐2 significantly increased BDNF mRNA levels in the frontal cortex, hippocampus and amygdala without reducing immobility; and most of these effects were reversed by NTX. This study is the first to provide evidence that endogenous opioids can upregulate BDNF mRNA expression through the DOR and MOR, and that leu‐ and met‐enkephalin have similar pharmacological profiles to synthetic DOR agonists in producing antidepressant‐like effects.