Journal
BRAIN RESEARCH
Volume 1069, Issue 1, Pages 172-181Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2005.11.005
Keywords
delta opioid receptor; antidepressant; forced swim test; BDNF; peptide; in situ hybridization
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Funding
- NIDA NIH HHS [P50 DA000254, K21 DA000254, DA13386, DA07281, DA00254, P01 DA000254, R01 DA013386, T32 DA007281] Funding Source: Medline
- NIMH NIH HHS [MH42251, P01 MH042251] Funding Source: Medline
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Systemically active, nonpeptidic delta opioid receptor agonists have been shown to produce antidepressant and anxiolytic effects in animal models in rodents. in addition, delta agonists have been shown to increase expression of brain-derived neurotrophic factor (BDNF) mRNA, an effect of some antidepressants, which may be important for the clinical efficacy of antidepressant drugs. The present study examined whether a variety of peptidic delta agonists, DPDPE, JOM-13, a systemically active derivative of DPDPE, deltorphin II, and H-Dmt-Tic-NH-CH2-Bid could produce convulsions and antidepressant-like effects in the forced swim test. In addition, some of these compounds were examined for their influence on BDNF mRNA expression. All four agonists dose-dependently decreased immobility in the forced swim test, indicating an antidepressant-like effect. Only JOM-13 produced convulsions at doses required for antidepressant-like effects. In addition, DPDPE increased BDNF mRNA expression, as measured by in situ hybridization, in the frontal cortex. The antidepressant-like effect of the agonists in the forced swim test and the increase in BDNF mRNA expression produced by DPDPE were blocked by the delta antagonist naltrindole. Therefore, activation of the delta receptor by centrally administered peptidic agonists and intravenously administered JOM-13 produces behavioral antidepressant-like effects without producing convulsions, and some peptidic agonists can increase BDNF mRNA expression, however, not as consistently as the systemically active nonpeptidic agonists. (c) 2005 Elsevier B.V. All rights reserved.
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