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)
Articles published in Agência FAPESP Newsletter about the research grant:
QUADIR, SEMA G.;
BORGES DOS SANTOS, JAQUELINE ROCHA;
CAMPBELL, RIANNE R.;
WROTEN, MELISSA G.;
HOLLOWAY, JOHN J.;
BAL, SUKHMANI K.;
SZUMLINSKI, KAREN K.
Homer2 regulates alcohol and stress cross-sensitization.
Web of Science Citations: 16.
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