Abstract
BACKGROUND: Methamphetamine (METH) is one of the most widely abused illicit substances around the world, unfortunately its addiction mechanism remains unclear. Increasing evidences indicate that the change of gene expression and the involvement of chromatin modifications might be related with the lasting effects of METH on the brain. In the study, we took advantage of METH-induced behavioral sensitization as the animal model that reflects some aspects of drug addiction, and examined the transcription and histone acetylation changes in gene expression in prefrontal cortex (PFC) of adult rats.
METHODS: We conducted the mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarrays (ChIP-chip) analysis to test and screen the transcriptional changes and histone acetylation modifications. The functional-enrichment analysis including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze the differential expression genes. We then further identified the alterations of ANP32A (Acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (The POU domain, class 3, transcription factor 2) by real-time PCR and ChIP-PCR assay.
RESULTS: In the rat model of METH-induced behavioral sensitization, challenge of METH caused 275 differentially expressed genes and a number of hyperacetylations (821 genes in H3 acetylation and 10 genes in H4 acetylation). We further tested the alteration of ANP32A and POU3F2 in transcription and histone acetylation at the different periods of this model, and revealed that histone acetylation modifications contributed to mRNA change of the genes expression caused by METH induced-behavioural sensitization while not by METH acute treatment.
CONCLUSIONS: the present results revealed an amount of alteration in transcription and histone acetylation in rat PFC by the exposure of METH, and provided the evidence that the modifications of histone acetylation is contributed to the alteration of the genes expression caused by METH-induced behavioural sensitization.
Differential Effects of Discrete Subarea-specific Lesions of the Rat Medial Prefrontal Cortex on Amphetamine- and Cocaine-induced Behavioural Sensitization
