RACK1 inhibits morphine re-exposure via inhibition of Src.
OBJECTIVE
We previously demonstrated that receptor for activated C kinase 1 (RACK1) inhibited phosphorylated extracellular signal-regulated kinase (p-ERK) during morphine reward in mice. In the present study, we examined the role of Src in regulating the inhibition of p-ERK in the brain following RACK1 over-expression during morphine reward.


METHODS
Mice were subcutaneously injected with morphine on days 2, 4, 6, and 8 after pre-test (day 1), and saline was delivered the following day. After mice showed place preference, RACK1 over-expression plasmid was administered by intraventricular injection 20 minutes after morphine injection on days 11 and 13. Conditioned place preference (CPP) was measured on days 14, 15, 19, and 20.


RESULTS
Chronic morphine injection increased Src and p-ERK expression in cortex and hippocampus, and mice exhibited increased place preference. Intraventricular administration of RACK1 reduced Src and p-ERK levels in cortex and hippocampus, as well as morphine reward. At 7 days of final RACK1 administration, the effects of RACK1 on Src and p-ERK disappeared, and morphine place preference was restored.


CONCLUSIONS
We demonstrated that RACK1 acts on ERK activation via Src in morphine reward in mice.
Liu
Qiaofeng
Q
Key Laboratory of Chronobiology, School of Huaxi Preclinical Medicine and Forensic Medicine, Sichuan University, Chengdu, China.
Wang
Xin
X
Liu
Yanyou
Y
Lu
Rui
R
Yuan
Quan
Q
Yang
Bin
B
Zhou
Jiang
J
Wang
Yuhui
Y
Wang
Zhengrong
Z
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection / Q000379:methods; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D009479:Neuropeptides; D010455:Peptides; C090294:RACK1 protein, mouse; D000075370:Receptors for Activated C Kinase; C070301:peptide I; D009020:Morphine; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases