Induction of the immediate early genes egr-1 and c-fos by methamphetamine in mouse brain

• Published in: Brain research Vol. 919; no. 1; pp. 31 - 40
• Main Authors: Thiriet, Nathalie, Zwiller, Jean, Ali, Syed F
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 16.11.2001; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; c-Fos gene; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Dopamine - metabolism; Dopamine Agents - administration & dosage; Dopamine Agents - pharmacology; Dose-Response Relationship, Drug; Drug addictions; Early Growth Response Protein 1; egr gene; egr-1, c-fos dopaminergic neurotoxicity; Gene Expression Regulation - drug effects; Genes, fos - drug effects; Genes, Immediate-Early - drug effects; Genes, Immediate-Early - physiology; Immediate early gene (IEG); immediate early genes; Immediate-Early Proteins; Injections, Intraperitoneal; Life Sciences; Male; Medical sciences; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - pharmacology; Mice; Mice, Inbred C57BL; monoamines; Retroviridae Proteins, Oncogenic - biosynthesis; Retroviridae Proteins, Oncogenic - genetics; RNA, Messenger - biosynthesis; Serotonin - metabolism; Time Factors; Toxicology; Transcription Factors; Transcriptional Activation; Disorders of the nervous system; egr-1, c-fos dopaminergic neurotoxicity; Immediate early gene (IEG); Methamphetamine; CNS stimulant; Induction; Rodentia; Central nervous system; Metamfetamine; Vertebrata; Mammalia; Mouse; Animal; Drug of abuse; Protooncogene; Brain (vertebrata); Immediate early gene
• ISSN: 0006-8993; 1872-6240; 0006-8993
• DOI: 10.1016/S0006-8993(01)02991-2

Methamphetamine (METH) is one of the most commonly abused psychostimulant, and is known to induce dopaminergic neurotoxicity by generating oxidative stress and free radicals. In the present study we investigated the effects of METH on egr-1 and c-fos immediate early gene induction in different regions of mouse brain, at different doses and different time courses. We also measured the tissue levels of monoamines in order to correlate their changes with gene expression. A single injection of METH (40 mg/kg) significantly increased egr-1 and c-fos mRNA expression within 30 min in frontal cortex, nucleus accumbens, caudate putamen, septum and CA1 region of hippocampus. Time course studies showed that in most cases, both genes were expressed within 30 min and decreased after 60 min. METH produced a significant decrease in striatal dopamine level, reaching a very low level after 24 h. Striatal serotonin level significantly increased and returned to control levels after 2 h. These data show that METH induced egr-1 and c-fos mRNA expression in selective brain areas, which correlated with an alteration in monoamines.