title: Increased expression of proenkephalin and prodynorphin mRNAs in the nucleus accumbens of compulsive methamphetamine taking rats.
abstract: Addiction is associated with neuroadaptive changes in the brain. In the present paper, we used a model of methamphetamine self-administration during which we used footshocks to divide rats into animals that continue to press a lever to get methamphetamine (shock-resistant) and those that significantly reduce pressing the lever (shock-sensitive) despite the shocks. We trained male Sprague-Dawley rats to self-administer methamphetamine (0.1 mg/kg/infusion) for 9 hours daily for 20 days. Control group self-administered saline. Subsequently, methamphetamine self-administration rats were punished by mild electric footshocks for 10 days with gradual increases in shock intensity. Two hours after stopping behavioral experiments, we euthanized rats and isolated nucleus accumbens (NAc) samples. Affymetrix Array experiments revealed 24 differentially expressed genes between the shock-resistant and shock-sensitive rats, with 15 up- and 9 downregulated transcripts. Ingenuity pathway analysis showed that these transcripts belong to classes of genes involved in nervous system function, behavior, and disorders of the basal ganglia. These genes included prodynorphin (PDYN) and proenkephalin (PENK), among others. Because PDYN and PENK are expressed in dopamine D1- and D2-containing NAc neurons, respectively, these findings suggest that mechanisms, which impact both cell types may play a role in the regulation of compulsive methamphetamine taking by rats.
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Jean Lud
authors.initials: JL
authors.lastname: Cadet
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Krasnova
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Walther
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Christie
authors.initials: C
authors.lastname: Brannock
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ladenheim
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McCoy
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Collector
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Oscar V
authors.initials: OV
authors.lastname: Torres
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Ndeah
authors.initials: N
authors.lastname: Terry
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Jayanthi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism; D004597:Electroshock; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D051765:Early Growth Response Transcription Factors; D004745:Enkephalins; D057093:Orphan Nuclear Receptors; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D008694:Methamphetamine; C033660:preproenkephalin