Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain.

The effects of acute and chronic morphine treatments on the expression of Ca2+/calmodulin dependent protein kinase II (CaMK II) gene in rat brain were investigated using in situ hybridization histochemistry. Our data showed that repeated, but not single morphine administration, resulted in significant up-regulation of the alpha-CaMK II gene expression in hippocampus and frontal cortex. We further studied the time courses of alpha-CaMK II gene expression in response to repeated morphine administration. After 3 days of consecutive morphine injections, the alpha-CaMK II mRNA levels exhibited a trend of up-regulation, and after 6 days of consecutive morphine injections it increased over 50-60% as compared with the control group. The alpha-CaMK II mRNA levels remained high 24 h after the cessation of chronic morphine treatment and returned to the control level 72 h later. However, changes of alpha-CaMK II gene levels mentioned above were not detected in amygdala or piriform cortex. Taken together, our data demonstrate that chronic morphine treatment region-specific up-regulates the levels of the alpha-CaMK II gene expression in hippocampus and frontal cortex.