title: Translational control of nicotine-evoked synaptic potentiation in mice and neuronal responses in human smokers by eIF2α.
abstract: Adolescents are particularly vulnerable to nicotine, the principal addictive component driving tobacco smoking. In a companion study, we found that reduced activity of the translation initiation factor eIF2α underlies the hypersensitivity of adolescent mice to the effects of cocaine. Here we report that nicotine potentiates excitatory synaptic transmission in ventral tegmental area dopaminergic neurons more readily in adolescent mice compared to adults. Adult mice with genetic or pharmacological reduction in p-eIF2α-mediated translation are more susceptible to nicotine's synaptic effects, like adolescents. When we investigated the influence of allelic variability of the Eif2s1 gene (encoding eIF2α) on reward-related neuronal responses in human smokers, we found that a single nucleotide polymorphism in the Eif2s1 gene modulates mesolimbic neuronal reward responses in human smokers. These findings suggest that p-eIF2α regulates synaptic actions of nicotine in both mice and humans, and that reduced p-eIF2α may enhance susceptibility to nicotine (and other drugs of abuse) during adolescence.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Memory and Brain Research Center, Baylor College of Medicine, Houston, United States.
authors.forename: Andon N
authors.initials: AN
authors.lastname: Placzek
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, United States.|Michael E. DeBakey Veteran Administration Medical Center, Houston, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Molfese
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Memory and Brain Research Center, Baylor College of Medicine, Houston, United States.|Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Khatiwada
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Memory and Brain Research Center, Baylor College of Medicine, Houston, United States.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Viana Di Prisco
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Memory and Brain Research Center, Baylor College of Medicine, Houston, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Carmela
authors.initials: C
authors.lastname: Sidrauski
authors.affiliation: Department of Physiology, McGill University, Montreal, Canada.
authors.forename: Krešimir
authors.initials: K
authors.lastname: Krnjević
authors.affiliation: Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, United States.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Amos
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Memory and Brain Research Center, Baylor College of Medicine, Houston, United States.
authors.forename: Russell
authors.initials: R
authors.lastname: Ray
authors.affiliation: Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School of Medicine, Philadelphia, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Dani
authors.affiliation: Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Walter
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, United States.|Michael E. DeBakey Veteran Administration Medical Center, Houston, United States.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Salas
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Memory and Brain Research Center, Baylor College of Medicine, Houston, United States.
authors.forename: Mauro
authors.identifier: http://orcid.org/0000-0002-9809-4732
authors.initials: M
authors.lastname: Costa-Mattioli
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009538:Nicotine / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012907:Smoking; D013569:Synapses / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000502:physiology*; D014026:Nicotiana
chemical_list: D015852:Eukaryotic Initiation Factor-2; D009538:Nicotine
keywords: adolescents; human; human fMRI; mouse; neuroscience; nicotine-induced plasticity; protein synthesis; ventral tegmental area