title: Repeated electroconvulsive seizure treatment in rats reduces inducibility of early growth response genes and hyperactivity in response to cocaine administration.
abstract: 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 10days (E10×) reduced Egr1, Egr2, Egr3, and c-fos mRNA and protein levels in the rat frontal cortex at 24h 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 5days 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.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hong Geun
authors.initials: HG
authors.lastname: Park
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Han Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Yong Min
authors.initials: YM
authors.lastname: Ahn
authors.forename: Ung Gu
authors.initials: UG
authors.lastname: Kang
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D051765:Early Growth Response Transcription Factors / Q000235:genetics*; D004597:Electroshock; D051638:Ether-A-Go-Go Potassium Channels / Q000096:biosynthesis / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D016762:Genes, fos / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; C400751:Cuzd1 protein, rat; D051765:Early Growth Response Transcription Factors; D051638:Ether-A-Go-Go Potassium Channels; C109500:Kcnh6 protein, rat; C109501:Kcnh7 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine