Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects
Jutkiewicz EM, Torregrossa MM, Sobczyk-Kojiro K, Mosberg HI,
Folk JE, Rice KC, Watson SJ, Woods JH.
1301 Medical Science Research Building III,
Department of Pharmacology,
University of Michigan Medical School,
Ann Arbor, MI 48109-0632, United States.
Eur J Pharmacol. 2006 Jan 24;


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.
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