Evaluation of CREB activation pathway in adolescent and adult mice treated with cocaine.

• Grant number: 12/10260-7
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2012 - December 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Rosana Camarini
• Grantee: Rosana Camarini
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Adolescents differ from adults in behavioral and neurochemical parameters. Studies from our laboratory showed a more marked sensitization to the locomotor stimulant effects induced by cocaine and more rapid onset of peak extracellular dopamine levels than adults. Pilot experiment also showed that cocaine abstinence led to an increase in anxiety-like behavior and CREB levels in the prefrontal cortex (PFC) in adolescent, but not in adult mice. Changes of the transcription factor CREB have been found in the dopaminergic mesolimbic circuit following cocaine exposure. CREB is regulated by several signaling pathways, such as PKA, CaMK and ERK. Overexpression of CREB in striatum reduces locomotor sensitization to cocaine, whereas mutations of CREB increased the conditioned place preference and behavioral sensitization to cocaine, showing a role of CREB in this phenomenon. The behavioral effects of CREB at the level of the nucleus accumbens (NAc) are mediated through the regulation of specific target genes. BDNF is one of those genes. BDNF has been implicated in neuroadaptations triggered by repeated cocaine exposure. In animal models of cocaine addiction, BDNF levels in the brain are elevated in cortical and subcortical areas relevant to addiction. This study will evaluate the locomotor sensitization and anxiety-like behaviors induced by cocaine, the CREB activation pathways, CREB levels, and the regulation of protein levels and gene expression of BDNF and its receptor TrKB in the PFC in adolescent and adult mice treated with cocaine. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARCOS PAUTASSI, RICARDO; SUAREZ, ANDREA B.; HOFFMANN, LUCAS BARBOSA; RUEDA, ANDRE VELOSO; RAE, MARIANA; MARIANNO, PRISCILA; CAMARINI, ROSANA. Effects of environmental enrichment upon ethanol-induced conditioned place preference and pre-frontal BDNF levels in adolescent and adult mice. SCIENTIFIC REPORTS, v. 7, AUG 17 2017. (12/10260-7, 15/02397-0)

CARRARA-NASCIMENTO, PRISCILA FERNANDES; HOFFMANN, LUCAS BARBOSA; FLORIO, JORGE CAMILO; PLANETA, CLEOPATRA SILVA; CAMARINI, ROSANA. Effects of Ethanol Exposure During Adolescence or Adulthood on Locomotor Sensitization and Dopamine Levels in the Reward System. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 14, MAR 6 2020. (12/17228-1, 15/02397-0, 12/10260-7, 17/11987-1, 18/05038-0)

CAMARINI, ROSANA; PAUTASSI, RICARDO MARCOS. Behavioral sensitization to ethanol: Neural basis and factors that influence its acquisition and expression. Brain Research Bulletin, v. 125, p. 53-78, JUL 2016. (10/12968-1, 07/07871-6, 12/10260-7)

CAMARINI, ROSANA; HOFFMANN, LUCAS BARBOSA; SUAREZ, ANDREA; RAE, MARIANA; MARCOURAKIS, TANIA; PAUTASSI, RICARDO MARCOS. Cocaine-induced behavioral sensitization is greater in adolescent than in adult mice and heightens cocaine-induced conditioned place preference in adolescents. Pharmacology Biochemistry and Behavior, v. 181, p. 60-68, JUN 2019. (17/11987-1, 12/10260-7)

CARRARA-NASCIMENTO, PRISCILA F.; HOFFMANN, LUCAS B.; CONTO, MARCOS B.; MARCOURAKIS, TANIA; CAMARINI, ROSANA. Ethanol Sensitization during Adolescence or Adulthood Induces Different Patterns of Ethanol Consumption without Affecting Ethanol Metabolism. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 11, MAR 23 2017. (12/10260-7, 12/17228-1)

QUADIR, SEMA G.; BORGES DOS SANTOS, JAQUELINE ROCHA; CAMPBELL, RIANNE R.; WROTEN, MELISSA G.; SINGH, NIMRITA; HOLLOWAY, JOHN J.; BAL, SUKHMANI K.; CAMARINI, ROSANA; SZUMLINSKI, KAREN K.. Homer2 regulates alcohol and stress cross-sensitization. ADDICTION BIOLOGY, v. 21, n. 3, p. 613-633, MAY 2016. (12/10260-7)