title: Changes in CREB activation in the prefrontal cortex and hippocampus blunt ethanol-induced behavioral sensitization in adolescent mice.
abstract: Drug dependence is a major health problem in adults and has been recognized as a significant problem in adolescents. We previously demonstrated that repeated treatment with a behaviorally sensitizing dose of ethanol in adult mice induced tolerance or no sensitization in adolescents and that repeated ethanol-treated adolescents expressed lower Fos and Egr-1 expression than adult mice in the prefrontal cortex (PFC). In the present work, we investigated the effects of acute and repeated ethanol administration on cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) DNA-binding activity using the electrophoretic mobility shift assay (EMSA) and the phosphorylated CREB (pCREB)/CREB ratio using immunoblotting in both the PFC and hippocampus in adolescent and adult mice. Adult mice exhibited typical locomotor sensitization after 15 days of daily treatment with 2.0 g/kg ethanol, whereas adolescent mice did not exhibit sensitization. Overall, adolescent mice displayed lower CREB binding activity in the PFC compared with adult mice, whereas opposite effects were observed in the hippocampus. The present results indicate that ethanol exposure induces significant and differential neuroadaptive changes in CREB DNA-binding activity in the PFC and hippocampus in adolescent mice compared with adult mice. These differential molecular changes may contribute to the blunted ethanol-induced behavioral sensitization observed in adolescent mice.
authors.affiliation: Department of Pharmacology, Instituto de Ciências Biomédicas, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Sabrina L
authors.initials: SL
authors.lastname: Soares-Simi
authors.affiliation: Department of Pharmacology, Instituto de Ciências Biomédicas, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Pastrello
authors.affiliation: Department of Physiology, Instituto de Biociências, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Zulma S
authors.initials: ZS
authors.lastname: Ferreira
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Yonamine
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Tania
authors.initials: T
authors.lastname: Marcourakis
authors.affiliation: Department of Pharmacology, Instituto de Ciências Biomédicas, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.affiliation: Department of Pharmacology, Instituto de Ciências Biomédicas, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Camarini
keywords: CREB; EMSA; adolescence; behavioral sensitization; mice