Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 531, Issue 1-3, Pages 151-159Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2005.12.002
Keywords
behavior forced swim test; RB101; brain-derived neurotrophic factor (Rat)
Categories
Funding
- NIDA NIH HHS [T32 DA07267, P50 DA000254, P01 DA000254, DA00254, T32 DA007267, K21 DA000254] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007767, T32 GM07767] Funding Source: Medline
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Nonpeptidic delta-opioid receptor agonists produce antidepressant-like effects in rodents, and compounds that inhibit the breakdown of endogenous opioid peptides have antidepressant-like effects in animal models. In this study, the behavioral effects of the enkephalinase inhibitor, RB101 (N-[(R, S)-2-benzyl-3 -[(S)(2-amino-4-methyl-thio)-butyldithio]-1-oxopropyl]-1-phenylanine benzyl ester), were examined. Specifically, the effects of RB101 on convulsive activity, locomotor activity, and anti depressant-like effects in the forced swim test were studied in Sprague-Dawley rats, and the opioid receptor types mediating these effects were examined by antagonist studies. In addition, the effects of RB101 on brain-derived neurotrophic factor (BDNF) mRNA expression were evaluated in relation to its antidepressant effects. RB101 produced delta-opioid receptor-mediated antidepressant effects (32 mg/kg i.v. and 100 mg/kg i.p.) and increased locomotor activity (32 mg/kg i.v.) in rats. RB101 did not produce convulsions or seizures and did not alter BDNF mRNA expression. In conclusion, RB101 has the potential to produce antidepressant effects without convulsions. Published by Elsevier B.V.
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