Antidepressant-type effects of endogenous enkephalins protected by systemic RB 101 are mediated by opioid δ and dopamine D1 receptor stimulation

Baamonde, Ana; Dauge, Valérie; Ruiz‐Gayo, Mariano; Fulga, Ion; Turcaud, Serge; Fournié‐Zaluski, Marie‐Claude; Roques, Bernárd P.

doi:10.1016/0014-2999(92)90356-9

Cited by 126 publications

(70 citation statements)

References 35 publications

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“…This antidepressant activity was blocked with the selective delta-opioid receptor antagonist naltrindole, but not with muselective doses of naltrexone nor the kappa-selective receptor antagonist, nor-BNI. These findings confirm previous studies demonstrating that the antidepressant-like effects of RB101 are delta-opioid receptor-mediated (Baamonde et al, 1992;Tejedor-Real et al, 1998). These results further support previous findings that mu-and kappa-opioid receptor activation does not produce antidepressant-like effects in the forced swim test in rats (Broom et al, 2002).…”

Section: Discussionsupporting

confidence: 92%

“…Enkephalinase inhibitors elevate levels of endogenous opioids that act at multiple opioid receptors; therefore, the receptor mediating this antidepressant activity was unknown. However, Baamonde et al (1992) and Tejedor-Real et al (1998) demonstrated that the selective delta-opioid receptor antagonist, naltrindole, blocked the antidepressant-like effects produced by the enkephalinase inhibitor RB101 in the learned helplessness model of depression in mice. To further support this finding, intravenous administration of the selective delta-opioid peptide BUBU (Tyr-D.Ser-(O-tert-butyl)-Gly-PheLeu-Thr(O-Tert-butyl-OH) demonstrated antidepressant-like effects in the learned helplessness paradigm (Tejedor-Real et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects

Jutkiewicz

Torregrossa

Sobczyk-Kojiro

et al. 2006

European Journal of Pharmacology

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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]-l-phenylalaninebenzyl 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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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects

Jutkiewicz

Torregrossa

Sobczyk-Kojiro

et al. 2006

European Journal of Pharmacology

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“…Such studies have demonstrated antidepressant activity with the opioid ligand cyclazocine (Fink et al 1970; open, placebo-controlled study) and with the opioid peptide ␤ -endorphin (Kline et al 1977; open study). Interestingly, the enkephalinase inhibitors RB101 and BL-2401 exert an antidepressant-like action in a learned helplessness assay in rats, presumably by inhibiting the degradation of endogenous opioids (Baamonde et al 1992;Kita et al 1997). The effect of RB101 was reversed by the ␦ -opioid receptor antagonist nal-…”

Section: The Present Study Examined the Effect Of Opioid Receptor Agomentioning

confidence: 99%

Nonpeptidic δ-opioid Receptor Agonists Reduce Immobility in the Forced Swim Assay in Rats

Broom

Jutkiewicz

Folk³

et al. 2002

Neuropsychopharmacology

166

122

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The present study examined the effect of opioid receptor agonists in the rat forced swim assay. The ␦ -opioid receptor agonists SNC80 (( ϩ )-4-[( ␣ R)-␣ -((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,Ndiethylbenzamide) and ( 7 ␣ ,5]classes of compounds have also been investigated and have potential antidepressant activity. One such class of agents is the opioids. Studies have been performed using a variety of different opioid system-enhancing agents that suggest an antidepressant role for opioid agonists. Such studies have demonstrated antidepressant activity with the opioid ligand cyclazocine (Fink et al. 1970; open, placebo-controlled study) and with the opioid peptide ␤ -endorphin (Kline et al. 1977; open study). Interestingly, the enkephalinase inhibitors RB101 and BL-2401 exert an antidepressant-like action in a learned helplessness assay in rats, presumably by inhibiting the degradation of endogenous opioids (Baamonde et al. 1992;Kita et al. 1997). The effect of RB101 was reversed by the ␦ -opioid receptor antagonist nal-

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“…The selective delta-opioid agonist Tyr-D-Ser-(O-C(CH 3 ) 3 )-Gly-Phe-Leu-Thr-(O-C(CH 3 ) 3 (BUBU) produced antidepressant-like effects in the learned helplessness model of depression (Tejedor-Real et al 1998). Similarly, increasing levels of endogenous delta-opioid peptides with enkephalinase inhibitors such as RB101 revealed antidepressant-like effects in models of depression in mice and rats (Baamonde et al 1992;Tejedor-Real et al 1998). More recently, the nonpeptidic delta-opioid agonists SNC80 and (+)BW373U86 displayed naltrindole (NTI)-sensitive antidepressant-like properties in the forced swim test in rats (e.g., Broom et al 2002a;Jutkiewicz et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats

et al. 2005

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Rationale-Delta-opioid agonists produce a number of behavioral effects, including convulsions, anti-nociception, locomotor stimulation, and antidepressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convulsive and antidepressant-like characteristics of these compounds is essential for their potential clinical use.Objective-The present study tests the hypothesis that the rate of delta-opioid agonist administration greatly contributes to the convulsive properties, but not the anti-depressant-like effects, of delta-opioid agonists.Materials and methods-The delta-opioid agonist SNC80 (1, 3.2, and 10 mg kg −1 or vehicle) was administered to Sprague-Dawley rats by intravenous infusion over different durations of time (20 s, 20, or 60 min). Convulsions were measured by observation prior to determining antidepressantlike effects in the forced swim test.Results-Slowing the rate of SNC80 administration minimized delta agonist-induced convulsions without altering the effects of SNC80 in the forced swim test.Conclusions-These data suggest that delta agonist-induced antidepressant properties are independent of convulsive effects, and that it may be possible to eliminate the convulsions produced by delta agonists, further promoting their potential clinical utility.

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Antidepressant-type effects of endogenous enkephalins protected by systemic RB 101 are mediated by opioid δ and dopamine D1 receptor stimulation

Cited by 126 publications

References 35 publications

Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects

Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects

Nonpeptidic δ-opioid Receptor Agonists Reduce Immobility in the Forced Swim Assay in Rats

Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats

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