Potential Anxiolytic and Antidepressant-Like Activities of SNC80, a Selective δ-Opioid Agonist, in Behavioral Models in Rodents

Saitoh, Akiyoshi; Kimura, Yuji; Suzuki, Tomohiko; Kawai, Koji; Nagase, Hiroshi; Kamei, Junzo

doi:10.1254/jphs.fpj04014x

Cited by 165 publications

(141 citation statements)

References 25 publications

(18 reference statements)

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“…Previous studies have shown that SNC80 produces anxiolytic effects in naive rats Saitoh et al, 2004). In the present study, SNC80 did not show a significant anxiolytic response in control animals that were injected with saline for 14 days.…”

Section: Discussioncontrasting

confidence: 51%

“…Pharmacological evidence for this hypothesis has been reported by our lab and others. The selective delta opioid receptor agonist SNC80 dose-dependently reduces anxiety- Saitoh et al, 2004) and depression-like (Jutkiewicz et al, 2003) behaviors. Conversely, the selective delta opioid receptor antagonist naltrindole can be anxiogenic in rodents (Marin et al, 2003;Perrine et al, 2006;Saitoh et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat

et al. 2008

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Chronic administration of cocaine has been shown to attenuate the functional capacity of delta opioid receptors to inhibit adenylyl cyclase activity. Abuse and withdrawal from cocaine in humans is associated with increases in anxiety and depression. Since recent research supports the role of delta opioid receptors in anxiety-and depression-like behaviors in rodents, we hypothesized that functional desensitization of delta opioid receptors contributes to anxiety-and depression-like behavioral phenotypes following short-term withdrawal from chronic administration of cocaine. To test this hypothesis, delta opioid receptor signaling and behaviors were evaluated 24 h after 14 days of bingepattern cocaine administration (15 mg/kg three times daily at 1 h intervals) in male Sprague Dawley rats. Results showed that the inhibition of adenylyl cyclase by delta opioid receptor agonists was attenuated in the frontal cortex, nucleus accumbens and caudate putamen 24 h after cessation of cocaine administration. One day withdrawal from chronic administration of cocaine resulted in increased anxiety-and depression-like behaviors as measured by the elevated plus maze and the force swim test respectively, and no change in locomotor activity. The anxiety-and depression-like behaviors were dose-dependently reduced by acute administration of the selective delta opioid receptor agonist, SNC80. These results demonstrate that early withdrawal from cocaine resulted in increased anxiety and depression, which accompanies the desensitization of delta opioid receptor function. Furthermore, cocaine-induced anxiety-and depression-like behaviors were reversible by the delta opioid receptor agonist SNC80.

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Section: Discussioncontrasting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat

et al. 2008

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“…We examined the effect of agonist treatment on the distribution of subcellular DOR-EGFP fluorescence in the knockin mice. We treated DOR-EGFP mice with either vehicle or SNC80 (10 mg͞kg s.c.), known to induce ␦ receptor-mediated behaviors (29,30). After 20 min, brains were removed, and receptor distribution was examined in six areas of the nervous system including central and peripheral sites (Fig.…”

Section: Resultsmentioning

confidence: 99%

Knockin mice expressing fluorescent δ-opioid receptors uncover G protein-coupled receptor dynamics in vivo

Scherrer

Tryoen-Tóth

Filliol

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

223

275

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The combination of fluorescent genetically encoded proteins with mouse engineering provides a fascinating means to study dynamic biological processes in mammals. At present, green fluorescent protein (GFP) mice were mainly developed to study gene expression patterns or cell morphology and migration. Here we used enhanced GFP (EGFP) to achieve functional imaging of a G proteincoupled receptor (GPCR) in vivo. We created mice where the ␦-opioid receptor (DOR) is replaced by an active DOR-EGFP fusion. Confocal imaging revealed detailed receptor neuroanatomy throughout the nervous system of knockin mice. Real-time imaging in primary neurons allowed dynamic visualization of drug-induced receptor trafficking. In DOR-EGFP animals, drug treatment triggered receptor endocytosis that correlated with the behavioral response. Mice with internalized receptors were insensitive to subsequent agonist administration, providing evidence that receptor sequestration limits drug efficacy in vivo. Direct receptor visualization in mice is a unique approach to receptor biology and drug design.behavioral desensitization ͉ green fluorescent protein ͉ neuroanatomy ͉ real-time imaging ͉ receptor internalization

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“…Although the anxiolytic properties of DOR selective agonists have been reported previously (Saitoh et al, 2004;Perrine et al, 2006;Jutkiewicz, 2007), the potential electrophysiological mechanisms by which these effects occur have yet to be investigated. Behaviorally, DOR knock-out mice display greater measures of anxiety than matched controls (Filliol et al, 2000), and selective ␦ antagonists can attenuate the anxiolytic actions of benzodiazepines (Primeaux et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

Margolis¹,

Fields²,

Hjelmstad³

et al. 2008

J. Neurosci.

106

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Alcoholism is a complex and debilitating syndrome affecting ϳ140 million people worldwide. However, not everyone who consumes ethanol develops abuse, raising the possibility that some individuals have a protective mechanism that inhibits elevated alcohol consumption. We tested the hypothesis that the ␦-opioid receptor (DOR) plays such a protective role. Here we show that DOR activity in the ventral tegmental area (VTA) robustly decreases ethanol consumption in rats and that these effects depend on baseline ethanol consumption. Intra-VTA microinjection of the DOR agonist DPDPE decreases drinking, particularly in low-drinking animals. Furthermore, VTA microinjection of the DOR selective antagonist TIPP-⌿ increases drinking in low, but not high, drinkers and this increase is blocked by comicroinjection of the GABA A antagonist bicuculline. Using electrophysiological techniques we found that in VTA brain slices from drinking rats DPDPE presynaptically inhibits GABA A receptor mediated IPSCs in low drinkers, but not in high drinkers or naive animals, most likely through activation of DORs on GABA terminals. This DOR-mediated inhibition of IPSCs also correlates inversely with behavioral correlates of anxiety measured in the elevated plus maze. In contrast, presynaptic inhibition of VTA GABA A IPSCs by theopioid receptor agonist DAMGO is significantly reduced in both high-and low-drinking rats (Ͻ30%) compared with age-matched nondrinking controls (Ͼ70%). Together, our findings demonstrate the protective nature of VTA DORs and identify an important new target for therapeutic intervention for alcoholism.

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Potential Anxiolytic and Antidepressant-Like Activities of SNC80, a Selective δ-Opioid Agonist, in Behavioral Models in Rodents

Cited by 165 publications

References 25 publications

Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat

Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat

Knockin mice expressing fluorescent δ-opioid receptors uncover G protein-coupled receptor dynamics in vivo

δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

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