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Cited by 55Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolCannabis and Cannabinoid Research

Maternal separation increases alcohol-drinking behaviour and reduces endocannabinoid levels in the mouse striatum and prefrontal cortex

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Portero-Tresserra, Marta, Gracia-Rubio, Irene, Cantacorps, Lídia, Pozo, Oscar J., Gómez-Gómez, Alejandro, Pastor, Antoni, López-Arnau, Raúl, de la Torre, Rafael +1 more·2018·European Neuropsychopharmacology
DOI 10.1016/j.euroneuro.2018.02.003
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Abstract

Childhood adversity is associated with an increased risk of mood, anxiety and substance use disorders. Maternal separation is a reliable rodent model of early life adversity that leads to depression-like symptoms, which may increase the vulnerability to alcohol consumption during adolescence. However, the specific alterations in the pattern of alcohol consumption induced by maternal separation and the underlying molecular mechanisms are still unclear. The purpose of this study is to evaluate the long-term effects of maternal separation with early weaning (MSEW) on emotional and social behaviour, alcohol rewarding properties, and alcohol consumption, abstinence and relapse in adolescent male C57BL/6 mice. In addition, endocannabinoid and monoamine levels were analysed in discrete brain areas. Results showed that MSEW mice presented emotional alterations related to depressive-like behaviour and modified endocannabinoid levels in the striatum and the prefrontal cortex. MSEW mice also showed impairments in alcohol-induced conditioned place preference and higher alcohol intake in a model of binge drinking. Moreover, MSEW animals displayed a higher propensity to relapse in the two-bottle choice paradigm following a period of alcohol abstinence associated with reduced monoamine levels in the striatum. Such results indicate that exposure to early life stress increased the vulnerability to alcohol binge-drinking during adolescence, which may be partially explained by decreased sensitivity to alcohol rewarding properties and the ability to potentiate alcohol intake following a period of abstinence.

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  • Neglected rodents exhibited significantly elevated corticosterone levels, indicating a dysregulated HPA axis response and heightened sensitivity to stress.

    “The same rodents also exhibited significantly elevated corticosterone levels, indicating a dysregulated HPA axis response and, thus, heightened sensitivity to stress.”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [146]

    The Results (section 3.4, p. 14) report significantly lower deoxycorticosterone (DOC) in maternally separated mice than in controls, not elevated levels. DOC is distinct from corticosterone, which the paper does not report measuring; the Introduction (p. 5) discusses heightened stress-hormone responsiveness as background, but does not establish the claimed result in these mice. (LLM, conf=0.86)

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  • Neglected rodent offspring have shown increased susceptibility to anxiety and depressive-like behaviors when exposed to stress in both adolescence and adulthood.

    “Neglected rodent offspring have shown increased susceptibility to anxiety and depressive-like behaviors when exposed to stress in both adolescence and adulthood (145, 146).”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [146]

    The Discussion (p. 15) reports despair-like behaviour and heightened social anxiety in adolescent mice exposed to maternal separation. It also mentions a previous report of reduced interest in social novelty in adult maternally separated mice, but does not establish increased anxiety and depressive-like behaviours in adulthood following a later stress exposure. (LLM, conf=0.83)

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Authors
Portero-Tresserra, M., Gracia-Rubio, I., Cantacorps, L., Pozo, O. J., Gómez-Gómez, A., Pastor, A., López-Arnau, R., de la Torre, R., & Valverde, O.
Affiliations
  • Universitat Pompeu Fabra (ES)
  • Municipal Institute for Medical Research (ES)
Corresponding author
Valverde, Olga
ORCID
Venue
European Neuropsychopharmacology
Publisher
Elsevier BV
Published
2018-04
Volume
28
Issue
4
Pages
499-512
ISSN
0924-977X (ISSN-L)
DOI
10.1016/j.euroneuro.2018.02.003
OpenAlex
W2794385501
Cited by
55
References
9
Citations by year
2026: 2 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 13 · 2020: 10 · 2019: 6 · 2018: 1
FWCI
3.43
Type
journal article
Language
en
Open access
Licence
Locations
  • European Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Zaguan (Universidad de Zaragoza) (acceptedVersion, other-oa)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion)
Funders
  • MINECO (SAF2016-75966-R)
  • Plan Nacional sobre Drogas (2014/020)
  • ISCIII and FEDER (CPII16/00027)
  • UE Medbioinformatic project (634143)
  • DIUE, Generalitat de Catalunya (2014SGR 680)
  • University of Barcelona
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Keywords
maternal separation, childhood adversity, early weaning, alcohol consumption, binge drinking, alcohol relapse, alcohol reward, endocannabinoid system, monoamines, striatum, prefrontal cortex, depression-like behavior, adolescent vulnerability, conditioned place preference, two-bottle choice
MeSH terms
Animals, Conditioning, Psychological, Corpus Striatum, Male, Maternal Deprivation, Mice, Inbred C57BL, Random Allocation, Reward, Social Behavior, Spatial Behavior, Stress, Psychological, Biogenic Monoamines, Prefrontal Cortex, Endocannabinoids, Binge Drinking

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