Adolescence: a time of transition for the phenotype of dcc heterozygous mice
Abstract
Rationale 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.Objectives 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.
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Striking, age-dependent differences can be reported in the enduring effects of the same experience on neural circuitry depending on the adolescent period in which this experience occurred.
“striking, age-dependent differences can be reported in the enduring effects of the same experience on neural circuitry depending on the adolescent period in which this experience occurred [48–51].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [48]
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- Authors
- Yetnikoff, L., Pokinko, M., Arvanitogiannis, A., & Flores, C.
- Affiliations
- McGill University (CA)
- Concordia University (CA)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Flores, Cecilia
- Venue
- Psychopharmacology
- Published
- 2013-04-10
- Volume
- 231
- Issue
- 8
- Pages
- 1705-1714
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2130987050
- Cited by
- 18
- References
- 43
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 1 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 1 · 2013: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Concordia University
- Fonds Québécois de la Recherche sur la Nature et les Technologies
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- DCC receptor, amphetamine sensitization, adolescence, ventral tegmental area, receptor expression, age-related susceptibility, resilience, developmental transitions
- MeSH terms
- DCC Receptor, Amphetamine, Central Nervous System Stimulants, Animals, Heterozygote, Male, Mice, Transgenic, Motor Activity, Phenotype, Random Allocation, Receptors, Cell Surface, Down-Regulation, Up-Regulation, Gene Expression, Rats, Wistar, Ventral Tegmental Area, Tumor Suppressor Proteins, Rats, Transgenic
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