Methamphetamine self‐administration alters gene expression in the rat striatum

Abstract

Striatum plays a critical role in the development of METH addiction but the molecular adaptations in the striatal neurons caused by METH exposure remain poorly understood. In the present study, we used an extended METH self‐administration model to study changes in gene expression in the rat striatum. Animals self‐administered METH (0.1 mg/kg/injection, i.v.) during 15‐hour sessions for 8 consecutive days. A yoked control group received passive injections of saline. The drug intake for the METH group reached 14.8 mg/kg/day. Rats were euthanized at 2 and 24 hours after the cessation of self‐administration. Transcriptional changes caused by METH were examined in the striatum using Illumina 22K Rat microarrays and validated by qRT‐PCR. METH self‐administration caused upregulation in the expression of transcription factors c‐fos, c‐jun, Nurr1, Nptx1 and neuropeptides cholecystokinin, neurotensin and neuromedin U. METH also induced increases in the expression of BDNF, synaptophysin, synaptotagmin II, syntaxin, cholinergic, glutamate and GABA receptors involved in the regulation of synaptic plasticity. Our results show that METH self‐administration causes changes in the expression of genes known to trigger persistent neuroadaptations in the mammalian brain. Some of these changes might contribute to METH‐related habit learning and development of METH addiction.