title: Disruption of acute opioid dependence by antisense oligodeoxynucleotides targeting neurogranin.
abstract: Neurogranin has been suggested to serve as a common regulator synchronizing the activities of PKC and CaMKII in acute opioid tolerance. To examine if a similar mechanism exists in acute opioid dependence, we directly targeted neurogranin using antisense oligodeoxynucleotides. Male ICR mice were pretreated with neurogranin antisense or mismatch oligodeoxynucleotides (2 microg/day, i.c.v.) for 3 consecutive days. On Day 4, morphine (100 mg/kg, s.c.) was used to induce dependence, as revealed by naloxone-precipitated withdrawal in saline or mismatch-pretreated mice. Antisense-pretreated mice showed decreased neurogranin expression, lack of morphine-induced phosphorylation of neurogranin and activation of CaMKII and CREB, and absence of naloxone-induced withdrawal jumping. Taken together, these data suggest that neurogranin plays an essential role in acute opioid dependence, possibly by affecting the CaMKII and CREB signaling pathway.
authors.affiliation: Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Zaijie Jim
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D007270:Injections, Intra-Articular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000209:etiology / Q000517:prevention & control*; D051579:Neurogranin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D013873:Thionucleotides / Q000008:administration & dosage*
chemical_list: D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D051579:Neurogranin; D009020:Morphine