Repeated electroconvulsive seizure treatment in rats reduces inducibility of early growth response genes and hyperactivity in response to cocaine administration

Regulated expression of immediate early genes (IEGs) in the brain reflects neuronal activity in response to various stimuli and recruits specific gene programs involved in long-term neuronal modification and behavioral alterations. Repeated electroconvulsive seizure (ECS) treatment reduces the expression level of several IEGs, such as c-fos, which play important roles in psychostimulant-induced behavioral changes. In this study, we investigated the effects of repeated ECS treatment on the basal expression level of IEGs and its effects on cocaine-induced activation of IEGs and locomotor activity in rats. Repeated ECS treatment for 10 days (E10×) reduced Egr1, Egr2, Egr3, and c-fos mRNA and protein levels in the rat frontal cortex at 24 h after the last ECS treatment, and these changes were evident in the neuronal cells of the prefrontal cortex. In particular, downregulation of Egr1 and c-fos was evident until 5 days after the last ECS treatment. Moreover, E10× pretreatment attenuated the cocaine-induced increase in Egr1, Egr2, and c-fos expression in the rat frontal cortex, whereas phosphorylation of ERK1/2, one of the representative upstream activators of these genes, increased significantly following cocaine treatment. Additionally, E10× pretreatment attenuated the increase in locomotor activity in response to a cocaine injection. In conclusion, repeated ECS treatment reduced the expression and inducibility of Egrs and c-fos, which could attenuate the response of the brain to psychostimulants.

Research Highlights
► Repeated treatments of ECS down-regulates Egr gene expression in rat frontal cortex.
► Reduced Egr1 expression lasts until 5 days after the end of repeated ECS treatments.
► Chronic ECS attenuates cocaine-induced Egr gene expression and hyperactivity of rats.