Toxic effect of calcium/calmodulin kinase II on anxiety behavior, neuronal firing and plasticity in the male offspring of morphine-abstinent rats.

Studies have shown that epigenetic changes such as alteration in histone acetylation and DNA methylation in various brain regions play an essential role in anxiety behavior. According to the critical role of calcium/calmodulin protein kinaseII (CaMKII) in these processes, the present study examined the effect of CaMKII inhibitor (KN93) on neuronal activity and level of c-fos in the amygdala and nucleus accumbens (NAC) in the offspring of morphine-exposed parents. Adult male and female Wistar rats received morphine orally (for 21 days). After the washout period (10 days), rats were mated with either drug-naïve or morphine-exposed rats. KN93 was microinjected into the brain of male offspring. The anxiety-like behavior, the neuronal firing rate in the NAC and the amygdala and level of c-fos were assessed by related techniques. Data showed the offspring with one and/or two morphine-abstinent parent(s) had more anxiety-like behavior than the control group. However, the administration of KN-93 decreased anxiety in the offspring of morphine-exposed rats compared with saline-treated groups. The expression level of the c-fos was not significantly altered by the inhibition of CaMKII in the amygdala, but the c-fos level was reduced in the NAC. The neuronal firing rate of these groups was associated with an increase in the amygdala in comparison to the saline groups but was decreased in the NAC. Results showed that CaMKII had a role in anxiety-like behavior in the offspring of morphine-exposed parents, and changes in neuronal firing rate and c-fos level in the NAC might be involved in this process.