title: Neuronal development genes are key elements mediating the reinforcing effects of methamphetamine, amphetamine, and methylphenidate.
abstract: BACKGROUND
  The molecular mechanisms underlying susceptibility to psychostimulant addiction remain unclear. Searching for commonalities in the effects of addictive drugs on brain gene expression is a prolific approach to determine transcriptional signatures influencing drug abuse.
  
  
  OBJECTIVE
  We explored the common transcriptional responses to the reinforcing effects of psychostimulants methamphetamine, amphetamine, and methylphenidate. We also aimed to identify transcriptional changes that may subserve abuse of these drugs.
  
  
  METHODS
  Genome-wide transcriptome profiling analyses were performed to identify common prefrontal cortical (PFC) and striatal gene expression profiles in drug-naïve (cohort 1) and stimulant-pretreated (cohort 2) rats, which showed a conditioned place preference to and self-administration of methamphetamine, amphetamine, and methylphenidate.
  
  
  RESULTS
  In behavioral studies, stimulant-pretreated rats showed behavioral sensitization characterized by enhanced behavioral response to the rewarding or reinforcing effects of psychostimulants. Inflammation-associated genes (e.g., Alas1, S100a8 and S100a9) were identified as the primary differentially expressed genes (DEGs) in both the PFC and the striatum of cohort 1 rats, while neuronal plasticity (Sgk1)- and brain development (e.g., Bhlhe22, Neurod1, Nr4a2, and Msx1)-associated genes comprised the major upregulated DEGs in the striatum of cohort 2 rats. Furthermore, a meta-analysis of the common striatal DEGs in this study along with morphine-regulated striatal transcriptomes in mice (National Center for Biotechnology Information-Gene Expression Omnibus Database Accession Code GSE7762) suggested similar expression profiles of genes involved in neuronal development (e.g., Bhlhe22, Nr4a2).
  
  
  CONCLUSIONS
  This study provides evidence that brain development-associated genes mediate the reinforcing effects of methamphetamine, amphetamine, and methylphenidate and that these transcripts may underlie susceptibility to psychostimulant addiction.
authors.affiliation: Uimyung Research Institute for Neuroscience, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815, Nowon-gu, Seoul, 139-742, South Korea.
authors.forename: Ike
authors.initials: I
authors.lastname: Dela Peña
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lee
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009020:Morphine; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D008694:Methamphetamine; D009020:Morphine; D000661:Amphetamine