Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The expression of opioid genes in non-classical reward areas depends on early life conditions and ethanol intake
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.ORCID iD: 0000-0002-8853-2508
Show others and affiliations
2017 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1668, p. 36-45Article in journal (Refereed) Published
Abstract [en]

The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e.g. dorsal striatum and amygdala, are highly responsive. The aim was to investigate the interaction between early life conditions and adult voluntary ethanol intake on opioid gene expression. Male Wistar rats were exposed to conventional rearing, 15, or 360min of daily maternal separation (MS) postnatal day 1-21, and randomly assigned to ethanol or water drinking postnatal week 10-16. Rats exposed to early life stress (MS360) had increased opioid receptor gene (Oprm1, Oprd1 and Oprk1) expression in the dorsal striatum. Ethanol drinking was associated with lower striatal Oprd1 and Oprk1 expression solely in rats exposed to early life stress. Furthermore, rats exposed to early life stress had high inherent Pomc expression in the amygdala but low expression after ethanol intake. Thus, adverse events early in life induced changes in opioid gene expression and also influenced the central molecular response to ethanol intake. These long-term consequences of early life stress can contribute to the enhanced risk for excessive ethanol intake and alcohol use disorder seen after exposure to childhood adversity.

Place, publisher, year, edition, pages
2017. Vol. 1668, p. 36-45
National Category
Neurosciences Neurology
Identifiers
URN: urn:nbn:se:uu:diva-330917DOI: 10.1016/j.brainres.2017.05.006ISI: 000404796300005PubMedID: 28511993OAI: oai:DiVA.org:uu-330917DiVA, id: diva2:1147641
Funder
Swedish Research Council, K2012-61X-22090-01-3; VR: 2015-00495The Swedish Brain FoundationLars Hierta Memorial FoundationForte, Swedish Research Council for Health, Working Life and WelfareEU, European Research Council, INCA 600398
Available from: 2017-10-06 Created: 2017-10-06 Last updated: 2018-03-16Bibliographically approved
In thesis
1. Stress, Drugs and Neuroscience: Neurobiological Effects of Social Stressors and Drug Exposure in Young and Adolescent Rats
Open this publication in new window or tab >>Stress, Drugs and Neuroscience: Neurobiological Effects of Social Stressors and Drug Exposure in Young and Adolescent Rats
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Experiences early in life or during adolescence modulate neuronal networks in the immature brain and consequently lay the foundation for future susceptibility or resilience towards psychiatric disorders. The objective in this thesis is to understand, in part, how the surrounding environment shapes the brain of a young individual. Three types of negative life events were studied, in an animal model, for their effects on the brain reward system (i.e., endogenous opioids and dopamine) and voluntary drug intake. These were: disruption of maternal care, disruption of interaction with peers, and exposure to drugs. Stress, in the form of maternal separation, altered expression of opioid genes in the dorsal striatum and amygdala, and the response to subsequent alcohol intake on these genes was dependent on early life conditions. Basal levels of endogenous opioids were also dependent on how the animals were housed in early adolescence. Short single housing (30 minutes) caused an acute stress response as evidenced by increased serum corticosterone and nociceptin/orphanin FQ in brain areas associated with stress. A prolonged single housing resulted in a marked decrease of Met-Enk-Arg6-Phe7 (i.e., a marker of enkephalins) in several brain areas. The endogenous opioids were also affected by repeated exposure of ethanol during adolescence; ethanol intoxication increased the accumbal levels of Met-Enk-Arg6-Pheand decreased those of β-endorphin. Residual effects of the adolescent ethanol exposure were found in Met-Enk-Arg6-Phe7 levels in the amygdala, ventral tegmental area, and substantia nigra. Furthermore, rats exposed to ethanol as adolescents had alterations in the dopamine dynamics in the dorsal striatum. Both endogenous opioids and dopamine are essential in mediating rewarding properties. Alterations of these systems, caused by environmental disturbances and alcohol exposure, presented herein could explain, in part, the increased susceptibility for alcohol- and substance use disorders later in life.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 79
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 253
Keyword
Adolescence, alcohol exposure, amphetamine, beta-endorphin, dopamine, dynorphin, early life, endogenous opioids, enkephalin, gene expression, high-speed chronoamperometry, nociceptin/orphanin FQ, radioimmunoassay, self-administration, social stress, voluntary alcohol intake
National Category
Substance Abuse Pharmacology and Toxicology Neurosciences
Research subject
Pharmaceutical Science
Identifiers
urn:nbn:se:uu:diva-346151 (URN)978-91-513-0282-9 (ISBN)
Public defence
2018-05-09, A1:107a, Biomedicinskt centrum, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2018-04-17 Created: 2018-03-16 Last updated: 2018-04-17

Open Access in DiVA

fulltext(449 kB)10 downloads
File information
File name FULLTEXT01.pdfFile size 449 kBChecksum SHA-512
d83730a9e7d8cb74d8b0b16d3b5bcc8257b5624f376bd0659fbd1245260aa0db4654d9e3c1d5b9dd949393c00337429fe494cb16065a503caf00d338531ab93d
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Granholm, LinneaNillson, KentComasco, ErikaNylander, Ingrid
By organisation
Department of Pharmaceutical BiosciencesNeuro-psycho-pharmacologyCentre for Clinical Research, County of Västmanland
In the same journal
Brain Research
NeurosciencesNeurology

Search outside of DiVA

GoogleGoogle Scholar
Total: 10 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 101 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf