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Role of Signalling Molecules in Behaviours Mediated by the δ Opioid Receptor Agonist SNC80

Role of Signalling Molecules in Behaviours Mediated by the δ Opioid Receptor Agonist SNC80

Isaac J Dripps, Brett T Boyer, Richard R Neubig, Kenner C Rice, John R Traynor, Emily M Jutkiewicz

Br J Pharmacol. 2018 Mar;175(6):891-901.

PMID: 29278419

Abstract:

Background and purpose:
GPCRs exist in multiple conformations that can engage distinct signalling mechanisms which in turn may lead to diverse behavioural outputs. In rodent models, activation of the δ opioid receptor (δ-receptor) has been shown to elicit antihyperalgesia, antidepressant-like effects and convulsions. We recently showed that these δ-receptor-mediated behaviours are differentially regulated by the GTPase-activating protein regulator of G protein signalling 4 (RGS4), which facilitates termination of G protein signalling. To further evaluate the signalling mechanisms underlying δ-receptor-mediated antihyperalgesia, antidepressant-like effects and convulsions, we observed how changes in Gαo or arrestin proteins in vivo affected behaviours elicited by the δ-receptor agonist SNC80 in mice.
Experimental approach:
Transgenic mice with altered expression of various signalling molecules were used in the current studies. Antihyperalgesia was measured in a nitroglycerin-induced thermal hyperalgesia assay. Antidepressant-like effects were evaluated in the forced swim test. Mice were also observed for convulsive activity following SNC80 treatment.
Key results:
In Gαo RGS-insensitive heterozygous knock-in mice, the potency of SNC80 to produce antihyperalgesia and antidepressant-like effects was enhanced with no change in SNC80-induced convulsions. Conversely, in Gαo heterozygous knockout mice, SNC80-induced antihyperalgesia was abolished while antidepressant-like effects and convulsions were unaltered. No changes in SNC80-induced behaviours were observed in arrestin 3 knockout mice. SNC80-induced convulsions were potentiated in arrestin 2 knockout mice.
Conclusions and implications:
Taken together, these findings suggest that different signalling molecules may underlie the convulsive effects of the δ-receptor relative to its antihyperalgesic and antidepressant-like effects.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP156727741	SNC80		156727-74-1	Price

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