| First Author | Dripps IJ | Year | 2017 |
| Journal | Psychopharmacology (Berl) | Volume | 234 |
| Issue | 1 | Pages | 29-39 |
| PubMed ID | 27624599 | Mgi Jnum | J:359333 |
| Mgi Id | MGI:7785717 | Doi | 10.1007/s00213-016-4432-5 |
| Citation | Dripps IJ, et al. (2017) The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors. Psychopharmacology (Berl) 234(1):29-39 |
| abstractText | 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 wild-type 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 [(3)H]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 in 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 may increase 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. |
