Dr. Zaijie Jim Wang and colleagues at the University of Illinois suppressed morphine tolerance and dependence in mice by blocking calcium/calmodulin-dependent protein kinase II (CaMKII), which may contribute to chronic pain in the central nervous system. In a followup study, the investigators found elevated levels of CaMKII activity in the brain and spinal cord (an 81 percent and 222 percent increase, respectively) of mice displaying morphine tolerance compared with mice that did not. Trifluoperazine, an antipsychotic drug and a CaMKII inhibitor newly identified by these researchers, prevented both the increase in CaMKII activity and the development of opioid tolerance and disrupted established opioid tolerance in the animals. The findings suggest that CaMKII-suppressing drugs may reduce morphine tolerance and ultimately be of value in treating pain and fighting opioid addiction.
Neuroscience Letters 397(1-2):1-4, 2006; [Abstract]
Journal of Pharmacology and Experimental Therapeutics 317(2): 901-909, 2006.