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.
Highlights
Epidemiological studies on drug consumption have revealed that ethanol is extensively consumed by adolescents (Degenhardt et al, 2008)
The present study showed age-related responses to ethanol in CREB binding activity and confirmed previous results from our laboratory, in which adolescent Swiss mice seem to be less sensitive to ethanol-induced behavioral sensitization than their adult counterparts (Faria et al, 2008; Camarini et al, 2010; Carrara-Nascimento et al, 2011, 2012)
This appear to be related to changes in behavioral sensitivity rather than ethanol pharmacokinetics, since blood ethanol concentrations (BECs) in adolescent and adult mice were similar after acute and repeated ethanol treatment
Summary
Epidemiological studies on drug consumption have revealed that ethanol is extensively consumed by adolescents (Degenhardt et al, 2008). Developmental changes are observed in the hippocampus and prefrontal cortex (PFC) in adolescents compared with adults (Giedd et al, 1996; De Bellis et al, 1999), such as a decrease in glutamatergic synapses and an increase in dopaminergic synapses in both regions. These brain regions are susceptible to the effects of alcohol in both human and rodent adolescents (De Bellis et al, 2000, 2005; Faria et al, 2008). An immature PFC is thought to be responsible for some of the typical behavioral characteristics of adolescents, such as Frontiers in Integrative Neuroscience www.frontiersin.org
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