Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine.
We have reported that ginseng total saponin (GTS) inhibited the development of physical and psychological dependence on morphine. However, the possible molecular mechanisms of GTS are unclear. Therefore, this study was undertaken to understand the possible molecular mechanism of GTS on the inhibitory effects of morphine-induced dependence. It has been reported that the up-regulated cAMP pathway in the LC of the mouse brain after repeated administration of morphine contributes to the feature of withdrawals. GTS inhibited up-regulation of cAMP pathway in the LC after repeated administration of morphine in this experiment. GTS inhibited cAMP levels and protein expression of protein kinase A (PKA). In addition, GTS inhibited the increase of cAMP response element binding protein (CREB) phosphorylation. Therefore, we conclude that the inhibitory effects of GTS on morphine-induced dependence might be mediated by the inhibition of cAMP pathway.
Seo
Jeong-Ju
JJ
College of Pharmacy, Chungbuk National University, Cheongju, 360-763, Korea.
Lee
Jae-Woong
JW
Lee
Wan-Kyu
WK
Hong
Jin-Tae
JT
Lee
Chong-Kil
CK
Lee
Myung-Koo
MK
Oh
Ki-Wan
KW
D000199:Actins / Q000096:biosynthesis; D000262:Adenylyl Cyclases / Q000378:metabolism; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D005894:Panax / Q000737:chemistry*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D000199:Actins; D000701:Analgesics, Opioid; D017362:Cyclic AMP Response Element-Binding Protein; D012503:Saponins; D009020:Morphine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases