Stress in adolescence and drugs of abuse in rodent models: role of dopamine, CRF, and HPA axis
Open accessAbstract
Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction-related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse.Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic-pituitary-adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms.Results and conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse.
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In rodents, adolescence is increasingly defined as the period from weaning (~PND 21) to neurobiological maturity around two months of age (~PND 60).
“adolescence in rodents is increasingly defined more in line with this larger age window in humans, by counting the period from weaning (~PND 21) where mice and rats gain begin to interact independently with their environments for the first time”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [46]
Section 2.1 (page not available) describes P21–P59 as the broadest definition of rodent adolescence and relates those stages to human adolescence. Section 4 says isolation rearing begins immediately after weaning, but the copy does not establish that P21 is when mice and rats first interact independently with their environments, or that use of this age window is increasing. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe week between PND21-28 has been described as the juvenile period, with PND21 identified as the lower boundary for early adolescence.
“The week between PND21 -28 has also been described as the juvenile period, with PND21 identified as the lower boundary for early adolescence (Burke and Miczek, 2014; Doremus-Fitzwater and Spear, 2016)”
From Age-dependent Effects of Tobacco Smoke and Nicotine on Cognition and the Brain: A Systematic Review of the Human and Animal Literature Comparing Adolescents and Adults. (2023) · cites this paper as Burke and Miczek, 2014
The adolescent period in rodents can be subdivided into early (~PND 21-34), middle (~PND 35-45), and late (~PND 45-60) periods.
“The adolescent period can be further sub-divided into early (~PND 21–34), middle (~PND 35–45), and late (~PND 45–60) periods [39, 46]”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [46]
Stress and the neurobiology of the stress response play critical roles in substance use initiation, maintenance, and relapse.
“Stress and the neurobiology of the stress response play critical roles in substance use initiation, maintenance, and relapse.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
BSRPs have been shown to be more effective than general health promotion interventions in reducing risky sexual behaviors and depression symptoms in MSMW with histories of childhood sexual abuse and current traumatic stress or depression.
“BSRPs have been shown to be more effective than general health promotion interventions in reducing risky sexual behaviors and depression symptoms in this population.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
HIV transmission risk is notably high among men who have sex with men and women, especially those with histories of childhood sexual abuse and current traumatic stress or depression.
“For instance, HIV transmission risk is notably high among men who have sex with men and women (MSMW), especially those with histories of childhood sexual abuse and current traumatic stress or depression.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
Stress mediators interact with the dopaminergic reward system and other systems involved in addiction, such as endogenous opioids, the SAM system, and endocannabinoids.
“Stress mediators interact with the dopaminergic reward system and other systems involved in addiction, such as endogenous opioids, the SAM system, and endocannabinoids.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
Emerging research highlights the role of stress in behavioral addictions, including hypersexual behavior, gambling, dysfunctional internet use, and food addiction.
“Emerging research highlights the role of stress in behavioral addictions, including hypersexual behavior, gambling, dysfunctional internet use, and food addiction.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
Adolescence is a critical period for the maturation of behavior, dopamine systems, and the HPA axis.
“Additionally, adolescence is a critical period for the maturation of behavior, dopamine systems, and the HPA axis.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
Stress during adolescence can increase sensitivity to drugs of abuse and alter the final maturation of cortical dopamine, potentially through mechanisms involving D2 dopamine receptor regulation and glucocorticoid-facilitated pruning of dopamine fibers.
“Stress during adolescence can increase sensitivity to drugs of abuse and alter the final maturation of cortical dopamine, potentially through mechanisms involving D2 dopamine receptor regulation and the glucocorticoid-facilitated pruning of dopamine fibers [83,84,85].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [83]
Individuals experiencing stressful events during early life and adolescence are particularly prone for developing cross-sensitization to drugs of abuse.
“In particular, evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence, suggesting that individuals experiencing stressful events during early life and adolescence are particularly prone for developing cross-sensitization to drugs of abuse (Burke & Miczek, 2014; Rodrigues et al., 2011).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Burke & Miczek, 2014
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- Authors
- Burke, A. R., & Miczek, K. A.
- Affiliations
- Tufts University (US)
- Corresponding author
- Burke, Andrew R.
- ORCID
- Miczek, Klaus A.
- Venue
- Psychopharmacology
- Published
- 2013-12-27
- Volume
- 231
- Issue
- 8
- Pages
- 1557-1580
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC3969449
- OpenAlex
- W2006049216
- Cited by
- 207
- References
- 291
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 11 · 2023: 12 · 2022: 17 · 2021: 21 · 2020: 15 · 2019: 11 · 2018: 30 · 2017: 21 · 2016: 17 · 2015: 24 · 2014: 8
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA013983)
- National Institute on Drug Abuse (F32DA032226, R01DA031734)
- National Institute of Neurological Disorders and Stroke (P30NS047243)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- adolescent stress, drugs of abuse, dopamine, corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, mesolimbic dopamine system, mesocortical dopamine, dopamine D2 receptor, glucocorticoid receptor, social stress, amphetamine, ethanol, cocaine, nicotine, locomotor sensitization, self-administration, rodent models
- MeSH terms
- Animals, Disease Models, Animal, Dopamine, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Rodentia, Illicit Drugs, Stress, Psychological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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