Dataset Information

Role of signalling molecules in behaviours mediated by the ? opioid receptor agonist SNC80.

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 ? opioid receptor (?-receptor) has been shown to elicit antihyperalgesia, antidepressant-like effects and convulsions. We recently showed that these ?-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 ?-receptor-mediated antihyperalgesia, antidepressant-like effects and convulsions, we observed how changes in G?_o or arrestin proteins in vivo affected behaviours elicited by the ?-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 G?_o 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 G?_o 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 ?-receptor relative to its antihyperalgesic and antidepressant-like effects.

SUBMITTER: Dripps IJ

PROVIDER: S-EPMC5825297 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Role of signalling molecules in behaviours mediated by the δ opioid receptor agonist SNC80.

Dripps Isaac J IJ Boyer Brett T BT Neubig Richard R RR Rice Kenner C KC Traynor John R JR Jutkiewicz Emily M EM

British journal of pharmacology 20180209 6

<h4>Background and purpose</h4>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 f ...[more]

PMID: 29278419

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