Kim, Juhwan Lee, Sueun Kang, Sohi Jeon, Tae-Il Kang, Man-Jong Lee, Tae-Hoon Kim, Yong Sik Kim, Key-Sun Im, Heh-In Moon, Changjong 2024-01-19T23:01:07Z 2024-01-19T23:01:07Z 2021-09-03 2018-05 1016-8478 https://pubs.kist.re.kr/handle/201004/121447 Crosstalk between G-protein signaling and glutamatergic transmission within the brain reward circuits is critical for long-term emotional effects (depression and anxiety), cravings, and negative withdrawal symptoms associated with opioid addiction. A previous study showed that Regulator of G-protein signaling 4 (RGS4) may be implicated in opiate action in the nucleus accumbens (NAc). However, the mechanism of the NAc-specific RGS4 actions that induce the behavioral responses to opiates remains largely unknown. The present study used a short hairpin RNA (shRNA)-mediated knock-down of RGS4 in the NAc of the mouse brain to investigate the relationship between the activation of ionotropic glutamate receptors and RGS4 in the NAc during morphine reward. Additionally, the shRNA-mediated RGS4 knock-down was implemented in NAc/striatal primary-cultured neurons to investigate the role that striatal neurons have in the morphine-induced activation of ionotropic glutamate receptors. The results of this study show that the NAc-specific knockdown of RGS4 significantly increased the behaviors associated with morphine and did so by phosphorylation of the GluR1 (Ser831) and NR2A (Tyr1325) glutamate receptors in the NAc. Furthermore, the knock-down of RGS4 enhanced the phosphorylation of the GluR1 and NR2A glutamate receptors in the primary NAc/striatal neurons during spontaneous morphine withdrawal. These findings show a novel molecular mechanism of RGS4 in glutamatergic transmission that underlies the negative symptoms associated with morphine administration. English KOREAN SOC MOLECULAR & CELLULAR BIOLOGY Regulator of G-Protein Signaling 4 (RGS4) Controls Morphine Reward by Glutamate Receptor Activation in the Nucleus Accumbens of Mouse Brain Article 10.14348/molcells.2018.0023 1 MOLECULES AND CELLS, v.41, no.5, pp.454 - 464 MOLECULES AND CELLS 41 5 454 464 N scie scopus kci ART002353672 000434131500009 2-s2.0-85055642285 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article KAPPA-OPIOID RECEPTORS MESSENGER-RNA PREFRONTAL CORTEX GENE-EXPRESSION DORSAL STRIATUM NMDA RECEPTORS MUTANT MICE C-FOS DOPAMINE DEPENDENCE addiction glutamatergic transmission morphine nucleus accumbensm regulator of G-protein signaling 4