NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension test through a delta-opioid receptor mechanism of action

Naidu, Pattipati S.; Lichtman, Aron H.; Archer, Carey C.; May, Everette L.; Harris, Louis S.; Aceto, Mario D.

doi:10.1016/j.ejphar.2007.03.031

Cited by 37 publications

(27 citation statements)

References 15 publications

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“…This report sought to expand on those findings and shows that RGS4 plays a complex role in regulating DOPr-mediated antidepressant-like effects, depending on the type of assay employed. In wild-type mice, SNC80 produced decreases in immobility in the forced swim and tail suspension tests, consistent with previous work showing that DOPr agonists produce antidepressant-like effects in these assays (Broom et al 2002a; Naidu et al 2007; Saitoh et al 2011). In both assays, SNC80 produced U-shaped dose effect curves, such that larger doses of SNC80 (10 mg/kg in TST, 32 mg/kg in FST) failed to produce significant antidepressant-like effects.…”

Section: Discussionsupporting

confidence: 91%

The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors

et al. 2016

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Rationale Regulator of G protein signaling (RGS) proteins act as negative modulators of G protein signaling. RGS4 has been shown to negatively modulate G protein signaling mediated by the delta opioid receptor (DOPr) in vitro. However, the role of RGS4 in modulating DOPr-mediated behaviors in vivo has not been elucidated. Objective The aim of this study was to compare the ability of the DOPr agonist SNC80 to induce DOPr-mediated antinociception, antihyperalgesia, antidepressant-like effects, and convulsions in wildtype and RGS4 knockout mice. Methods Antinociception was assessed in the acetic acid stretch assay. Antihyperalgesia was measured in a nitroglycerin-induced thermal hyperalgesia assay. Antidepressant-like effects were evaluated in the forced swim and tail suspension tests. Mice were also observed for convulsive activity post-SNC80 treatment. SNC80-induced phosphorylation of MAP kinase in striatal tissue from RGS4 wild-type and knockout mice was quantified by Western blot. DOPr number from forebrain tissue was measured using [3H]DPDPE saturation binding. Results Elimination of RGS4 potentiated SNC80-induced antinociception and antihyperalgesia. SNC80-induced antidepressant-like effects were potentiated in RGS4 knockout mice in the forced swim test but not the tail suspension test. Additionally, RGS4 knockout did not alter SNC80-induced convulsions. SNC80-induced phosphorylation of MAP kinase was potentiated in striatum from RGS4 knockout mice. Loss of RGS4 did not affect total DOPr number. Conclusions Overall, these findings demonstrate that reduction of RGS4 functionally increases the therapeutic index of SNC80. These results provide the first evidence of differential regulation of DOPr-mediated behaviors by RGS proteins and G protein signaling pathways.

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Section: Discussionsupporting

confidence: 91%

The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors

et al. 2016

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“…Several selective DOP receptor agonists reduced depressive-like behaviors in animal tests, including SNC80, NIH11082, UFP512, KNT-127, and AZD2327 [for a review, see (Chung and Kieffer, 2013)]. The antidepressant-like effects were comparable to those produced by selective serotonin reuptake inhibitors and tricyclic antidepressants (Naidu et al, 2007; Saitoh et al, 2004). DOP receptor agonists decreased anxiety- and depression-like behaviors in mice withdrawn from alcohol and cocaine (Ambrose-Lanci et al, 2010; Perrine et al, 2008; van Rijn et al, 2010)…”

Section: Introductionmentioning

confidence: 99%

Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test

Huang

Tunis

Parry

et al. 2016

European Journal of Pharmacology

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Kappa opioid (KOP) receptor antagonists and delta opioid (DOP) receptor agonists have antidepressant-like effects in animal tests and may be useful for treatment-resistant depression in humans. In this study, we examined whether the combination of a KOP receptor antagonist and a DOP receptor agonist would produce a better than additive effect (i.e. synergy). LY2444296 is a short-acting selective nonpeptide KOP receptor antagonist. ADL5859 is a selective nonpeptide DOP receptor agonist which does not produce seizures and EEG disturbances. Each compound and combinations of the two were examined in the forced swim test (FST) one h post injection, a screening test for antidepressant-like effect, in male adult C57BL/6J mice (Jackson Lab). LY2444296 [subcutaneous (s.c.) injection] at 10 and 30 mg/kg, but not 3 mg/kg, significantly decreased immobility time in a dose-dependent manner. Intraperitoneal (i.p.) injections of ADL5859 also reduced immobility time dose-dependently at doses of 3 and 10 mg/kg, but not at 1 mg/kg. An analysis was conducted using the method of Tallarida and Raffa (2010), which employed dose equivalence. The relative potency of the drugs was determined to be LY2444296: ADL5859=1:0.28, which was the dose ratio for combination studies. Six combinations of the two compounds were tested in mice at a fixed dose ratio. We found that LY2444296 and ADL5859 yielded significant synergistic effects for the antidepressant-like effect at the combined dose ranging from 3.84 mg/kg to 9.0 mg/kg. ADL5859 (10 mg/kg), LY2444296 (30 mg/kg) and their combined dose (3.84 mg/kg) had no effects on locomotor activities. Since the two drugs have distinct pharmacological profiles, such a synergism will allow use of lower doses of both drugs to achieve desired antidepressant effects with fewer side effects.

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“…97 The list includes more than a dozen agonists, from a variety of chemical structural classes. 69,[98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115] Interestingly, at least one study suggests that the antidepressant activity of the tricyclic antidepressant imipramine might be mediated by DOR. 116 Concomitantly, it has been suggested that the effects of tricyclic antidepressants on neuropathic pain require DOR stimulation, at least in mice.…”

Section: Other Therapeutic Potentialmentioning

confidence: 99%

Delta opioid agonists: a concise update on potential therapeutic applications

Peppin

Raffa

2015

J Clin Pharm Ther

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SUMMARYWhat is known and objective: The endogenous opioid system co-evolved with chemical defences, or at times symbiotic relationships, between plants and other autotrophs and heterotrophic predators -thus, it is not surprising that endogenous opioid ligands and exogenous mimetic ligands produce diverse physiological effects. Among the endogenous opioid peptides (endomorphins, enkephalins, dynorphins and nociception/orphanin FQ) derived from the precursors encoded by four genes (PNOC, PENK, PDYN and POMC) are the pentapeptides Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Leu-enkephalin (Tyr-Gly-Gly-PheLeu). The physiological effects of the enkephalins are mediated via 7-transmembrane G protein-coupled receptors, including delta opioid receptor (DOR). We present a concise update on the status of progress and opportunities of this approach. Methods: A literature search of the PUBMED database and a combination of keywords including delta opioid receptor, analgesia, mood and individual compounds identified therein, from industry and other source, and from www.clinicaltrials.com. Results and discussion: DOR agonist and antagonist ligands have been developed with ever increasing affinity and selectivity for DOR over other opioid receptor subtypes and studied for therapeutic utility, primarily for pain relief, but also for other clinical endpoints. What is new and conclusion: Selective DOR agonists have been designed with a large increase in therapeutic window for a variety of potential CNS applications including pain, depression, and learning and memory among others. WHAT IS KNOWN AND OBJECTIVE

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NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension test through a delta-opioid receptor mechanism of action

Cited by 37 publications

References 15 publications

The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors

The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors

Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test

Delta opioid agonists: a concise update on potential therapeutic applications

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