title: Adolescence: a time of transition for the phenotype of dcc heterozygous mice.
abstract: BACKGROUND
  Stark differences exist between adult (>PND 70) and juvenile (∼PND 21-34) rodents in how DCC (deleted in colorectal cancer) receptors and sensitization to amphetamine interact. In adults, repeated amphetamine upregulates DCC receptor expression selectively in the ventral tegmental area (VTA), an effect that is critical for sensitization. In contrast, amphetamine administered to juveniles downregulates VTA DCC expression. Moreover, whereas adult dcc heterozygous mice fail to sensitize when repeatedly treated with amphetamine, drug treatment during the juvenile period actually abolishes this adult "protective" phenotype.
  
  
  OBJECTIVE
  We set out to determine whether adolescence (PND ∼35-55) is a period during which: (1) amphetamine-induced alterations in VTA DCC expression switch from downregulation to upregulation; (2) the "protective" phenotype of adult dcc heterozygotes against sensitization becomes evident; and (3) the adult "protective" phenotype of dcc heterozygotes can still be abolished by repeated amphetamine treatment.
  
  
  RESULTS
  Repeated amphetamine did not significantly alter VTA DCC expression in adolescent rodents when assessed 1 week later. Both wild-type and dcc heterozygous mice exhibited sensitization at this time. Remarkably, wild-type mice, but not dcc heterozygotes, exhibited sensitization when tested during adulthood.
  
  
  CONCLUSIONS
  Adolescence is a time of transition for dcc heterozygotes as related to sensitization. Our results support the hypothesis that DCC may be a key factor in determining age-dependent individual differences in vulnerability to sensitization. Given that exposure to drugs of abuse during adolescence can have profound consequences for adulthood, the resilience of adult dcc heterozygous mice against adolescent exposure to amphetamine is particularly salient.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.
authors.forename: Leora
authors.initials: L
authors.lastname: Yetnikoff
authors.forename: Matthew
authors.initials: M
authors.lastname: Pokinko
authors.forename: Andreas
authors.initials: A
authors.lastname: Arvanitogiannis
authors.forename: Cecilia
authors.initials: C
authors.lastname: Flores
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D000075389:DCC Receptor; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006579:Heterozygote; D008297:Male; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D011897:Random Allocation; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D000075389:DCC Receptor; C501910:Dcc protein, mouse; C501912:Dcc protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000661:Amphetamine