title: Amphetamine elevates phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the rat forebrain via activating dopamine D1 and D2 receptors.
abstract: Psychostimulants have an impact on protein synthesis, although underlying molecular mechanisms are unclear. Eukaryotic initiation factor 2α-subunit (eIF2α) is a key player in initiation of protein translation and is regulated by phosphorylation. While this factor is sensitive to changing synaptic input and is critical for synaptic plasticity, its sensitivity to stimulants is poorly understood. Here we systematically characterized responses of eIF2α to a systemic administration of the stimulant amphetamine (AMPH) in dopamine responsive regions of adult rat brains. Intraperitoneal injection of AMPH at 5mg/kg increased eIF2α phosphorylation at serine 51 in the striatum. This increase was transient. In the medial prefrontal cortex (mPFC), AMPH induced a relatively delayed phosphorylation of the factor. Pretreatment with a dopamine D1 receptor antagonist SCH23390 blocked the AMPH-stimulated eIF2α phosphorylation in both the striatum and mPFC. Similarly, a dopamine D2 receptor antagonist eticlopride reduced the effect of AMPH in the two regions. Two antagonists alone did not alter basal eIF2α phosphorylation. AMPH and two antagonists did not change the amount of total eIF2α proteins in both regions. These results demonstrate the sensitivity of eIF2α to stimulant exposure. AMPH possesses the ability to stimulate eIF2α phosphorylation in striatal and mPFC neurons in vivo in a D1 and D2 receptor-dependent manner.
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, MO 64108, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors.forename: Cole A
authors.initials: CA
authors.lastname: Fitzgerald
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, MO 64108, USA.
authors.forename: Dao-Zhong
authors.initials: DZ
authors.lastname: Jin
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, MO 64108, USA.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Mao
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, MO 64108, USA; Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA. Electronic address: wangjq@umkc.edu.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Wang
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists / Q000008:administration & dosage; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000008:administration & dosage
chemical_list: D001552:Benzazepines; D000697:Central Nervous System Stimulants; D065127:Dopamine D2 Receptor Antagonists; D015852:Eukaryotic Initiation Factor-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D012457:Salicylamides; D000661:Amphetamine; C045989:eticlopride
keywords: Caudate putamen; Dopamine receptor; Initiation factor; Nucleus accumbens; Protein synthesis; Translation