Attenuation of opioid tolerance by antisense oligodeoxynucleotides targeting neurogranin.

Neurogranin is capable of regulating protein kinase C and Ca2+/calmodulin-dependent protein kinase II. In this study, we examined the role of neurogranin in opioid tolerance. Increased phosphorylation of neurogranin was found in opioid tolerance. Opioid tolerance was absent in morphine (100 mg/kg)-treated mice that were also pretreated with neurogranin antisense oligodeoxynucleotides (2 microg/day, i.c.v. for 3 days). The behavioral effect correlated with the decreased expression of neurogranin. These data suggest that neurogranin may be critical in the development of opioid tolerance.