Abstract
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]-l-phenylalanine benzyl ester), were examined. Specifically, the effects of RB101 on convulsive activity, locomotor activity, and antidepressant-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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adrenocorticotropic Hormone / blood
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Animals
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Antidepressive Agents / pharmacology*
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Behavior, Animal / drug effects*
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Benzamides / pharmacology
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Brain-Derived Neurotrophic Factor / blood
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Brain-Derived Neurotrophic Factor / genetics
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Disulfides / pharmacology*
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Dose-Response Relationship, Drug
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Electroencephalography / drug effects*
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Enzyme Inhibitors / pharmacology
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Frontal Lobe / metabolism
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Hippocampus / metabolism
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Injections, Intravenous
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Male
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Motor Activity / drug effects
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Neprilysin / antagonists & inhibitors*
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Phenylalanine / analogs & derivatives*
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Phenylalanine / pharmacology
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Piperazines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Swimming
Substances
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Antidepressive Agents
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Benzamides
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Brain-Derived Neurotrophic Factor
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Disulfides
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Enzyme Inhibitors
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Narcotic Antagonists
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Piperazines
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RNA, Messenger
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RB 101
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4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
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Phenylalanine
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Naltrexone
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Adrenocorticotropic Hormone
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Neprilysin
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naltrindole