Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm.
The present study was designed to determine the changes of phosphorylation of cAMP- response element binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204) in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204 displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for a long time without affecting total CREB protein levels. The effect of F9204 was similar to morphine which effect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitive N-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phosphorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also the phosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterations in the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence. NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.
Gao
Can
C
Second Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Che
Li Wei
LW
Chen
Jie
J
Xu
Xue Jun
XJ
Chi
Zhi Qiang
ZQ
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000378:metabolism; D010766:Phosphorylation; D012201:Reward; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D019966:Substance-Related Disorders / Q000209:etiology
D000700:Analgesics; D017362:Cyclic AMP Response Element-Binding Protein; D007649:Ketamine; D009020:Morphine; C037016:F 7302; D005283:Fentanyl