Maturation of coordinated immediate early gene expression by cocaine during adolescence.
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.
Caster
J M
JM
Department of Pharmacology and Cancer Biology, Research Park Building 2, Room 100B, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
Kuhn
C M
CM
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development*; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D003042:Cocaine