Maturation of coordinated immediate early gene expression by cocaine during adolescence.

Journal Article (Journal Article)

Adolescence may be a critical period for drug addiction. Young adolescent male rats have greater locomotor responses than adults after acute low dose cocaine administration. Further, repeated cocaine administration produces as much or more conditioned place preference but reduced locomotor sensitization in adolescents compared to adults. Acute activation of neurons by cocaine induces long-term changes in behavior by activating transcriptional complexes. The purpose of the present study was to correlate cocaine-induced locomotor activity with neuronal activation in subregions of the striatum and cortex by acute cocaine in young adolescent (postnatal (PN) 28) and adult (PN 65) male rats by measuring the induction of the plasticity-associated immediate early genes (IEGs) c-fos and zif268 using in situ hybridization. Animals were treated with saline, low (10 mg/kg), or high (40 mg/kg) dose cocaine in locomotor activity chambers and killed 30 min later. Low dose cocaine induced more locomotor activity and striatal c-fos expression in adolescents than adults whereas high dose cocaine induced more locomotor activity, striatal c-fos, and striatal zif268 expression in adults. Locomotor activity correlated with the expression of both genes in adults but correlated with striatal c-fos only in adolescents. Finally, there was a significant correlation between the expression of c-fos and zif268 in the adult striatum but not in adolescents. Our results suggest that the coordinated expression of transcription factors by cocaine continues to develop during adolescence. The immature regulation of transcription factors by cocaine could explain why adolescents show unique sensitivity to specific long-term behavioral alterations following cocaine treatment.

Full Text

Duke Authors

Cited Authors

  • Caster, JM; Kuhn, CM

Published Date

  • April 21, 2009

Published In

Volume / Issue

  • 160 / 1

Start / End Page

  • 13 - 31

PubMed ID

  • 19245875

Pubmed Central ID

  • PMC2668738

Electronic International Standard Serial Number (EISSN)

  • 1873-7544

Digital Object Identifier (DOI)

  • 10.1016/j.neuroscience.2009.01.001


  • eng

Conference Location

  • United States