Withdrawal from chronic drug treatment has differential effects on CaMKII activity. In rats, methamphetamine withdrawal does not alter CaMKII activity in the parietal cortex, NAc, or striatum, but a subsequent challenge dose of methamphetamine reduces CaMKII activity in these brain regions to a greater degree in methamphetamine-withdrawn rats compared with drug-naïve rats.239 Naloxone-precipitated morphine withdrawal increases autophosphorylation of CaMKIIα and CaMKIIβ in mouse cingulate cortex.249 Precipitated and unprecipitated withdrawal increase CaMKII activity and CaMKIIβ protein and mRNA, but not CaMKIIα protein or mRNA, in the rat hippocampus.250 Instead unprecipitated morphine withdrawal decreases autophosphorylated CaMKIIα in synaptosomal fractions of rat hippocampus.248
