uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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
Short and prolonged periods of maternal separation and voluntary ethanol intake in male and female ethanol-preferring AA and ethanol-avoiding ANA rats
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 Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2005 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 29, no 4, 591-601 p.Article in journal (Refereed) Published
Description
Abstract [en]

BACKGROUND: Genetic as well as environmental factors can affect the propensity for psychopathology and/or drug dependence. Maternal separation represents an animal experimental model that is useful in studies of effects of early life experiences. The authors have established a protocol for short and prolonged periods of maternal separation to study adult neurochemistry, behavior, and ethanol intake and have previously reported alterations in ethanol intake in Wistar rats and ethanol-preferring rats. The aim of the current study was to more thoroughly study how early life experiences affect an inherited propensity for high and low ethanol intake, respectively, in male and female ethanol-preferring AA (Alko alcohol) and ethanol-avoiding ANA (Alko, Non-Alcohol) rats. METHODS: AA and ANA pups were assigned to one of three different rearing conditions: 15 min (MS15) or 360 min (MS360) of daily maternal separation in litters or normal animal facility rearing (AFR) during postnatal days 1 to 21. In adulthood, voluntary ethanol intake was investigated using the two-bottle free choice paradigm. RESULTS: In male ethanol-preferring AA rats, MS15 resulted in a lower intake and fewer high-preferring animals at 8% and 10% ethanol compared with MS360 rats. The male MS360 rats had a higher ethanol intake at 8% and 10% ethanol in comparison with AFR rats. In contrast, the female AA MS15 and MS360 rats had a lower ethanol intake and a lower preference for the 10% ethanol solution compared with the female AA AFR rats. In male and female ANA rats, no major separation-induced effects were found. CONCLUSIONS: The current results show that genetic inheritance can be affected by environmental manipulations in AA rats with an inherent high ethanol intake. The findings in female ethanol-preferring AA rats give further evidence of a differential outcome of maternal separation in male and female rats, as previously shown.

Place, publisher, year, edition, pages
2005. Vol. 29, no 4, 591-601 p.
Keyword [en]
handling, maternal deprivation, alcohol, estrous cycle, sex differences
National Category
Pharmaceutical Sciences Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95646DOI: 10.1097/01.ALC.0000158933.70242.FCPubMedID: 15834224OAI: oai:DiVA.org:uu-95646DiVA: diva2:169946
Available from: 2007-03-30 Created: 2007-03-30 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Maternal Separation in Rats: An Experimental Model for Long-Term Effects of Early Life Experiences on Neurochemistry, Voluntary Ethanol Intake and Exploration and Risk Assessment Behavior
Open this publication in new window or tab >>Maternal Separation in Rats: An Experimental Model for Long-Term Effects of Early Life Experiences on Neurochemistry, Voluntary Ethanol Intake and Exploration and Risk Assessment Behavior
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The period of early life is important for the development of individual brain function and behavior. Human studies have shown altered vulnerability to develop psychopathology and/or excessive drug intake, possibly leading to dependence, as a consequence of early life experiences. In the present thesis, maternal separation (MS), an experimental model for studies of early environmental influences, was used to investigate long-term effects on neurochemistry, voluntary ethanol intake and exploration and risk assessment behavior in rats. Rat pups were assigned to one of three different rearing conditions: daily 15 min (MS15) or 360 min (MS360) of MS and normal animal facility rearing (AFR) during the first three weeks of life. Measurements of adult endogenous opioid peptide levels, opioid- and dopamine receptor density revealed minor MS-induced effects on the opioid system whereas interesting alterations were found in dopamine receptor density. Long-term effects on voluntary ethanol intake showed distinct MS-induced alterations in male Wistar and ethanol-preferring AA (Alko, Alcohol) rats. Female Wistar rats were unaffected, indicating sex differences in the effects of MS on ethanol intake. Male MS15 rats generally had a slower acquisition phase and a low subsequent ethanol intake whereas male MS360 rats had a high ethanol intake. MS15 is therefore suggested to protect against a high voluntary ethanol intake in male rats whereas MS360 may serve as a risk factor. The recently established concentric square field test indicated alterations in risk assessment as well as an increased exploratory drive and somewhat higher risk-taking behavior in adult MS360 rats, while minor effects were seen in MS15 rats. Altogether, these results demonstrate that environmental influences during the period of early life can have long-term effects on neurochemistry and behavior. Of special interest is the finding that MS altered the inherited high ethanol intake in adult ethanol-preferring AA rats.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 81 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 313
Keyword
Pharmaceutical pharmacology, Handling, Maternal Deprivation, Environment, Opioids, Dopamine, Alcohol, Stress, Concentric Square Field, Open Field, Elevated Plus-maze, Farmaceutisk farmakologi
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-4465 (URN)91-554-6009-7 (ISBN)
Public defence
2004-09-24, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2004-09-03 Created: 2004-09-03 Last updated: 2009-06-02Bibliographically approved
2. Endogenous Opioids and Voluntary Ethanol Drinking: Consequences of Postnatal Environmental Influences in Rats
Open this publication in new window or tab >>Endogenous Opioids and Voluntary Ethanol Drinking: Consequences of Postnatal Environmental Influences in Rats
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genetic and environmental factors interact to determine the individual vulnerability to develop ethanol dependence. The neurobiological mechanisms underlying these processes are not fully understood. Endogenous opioid peptides have been suggested to contribute. Brain opioids mediate ethanol reward and reinforcement via actions on the mesocorticolimbic dopamine system. This thesis focuses on environmental factors and investigates the impact of the early-life environment on adult voluntary ethanol consumption. The possible involvement of opioid peptides in environmental influences on adult ethanol consumption was examined using an experimental animal model.

Maternal separation with short 15 min separations (MS15) was used to simulate a safe environment whereas prolonged 360 min separations (MS360) simulated an unsafe environment. Control rats were subjected to normal animal facility rearing (AFR). The separations were performed daily from postnatal day 1 to 21. Long-term ethanol consumption was registered using a two-bottle or a four-bottle free-choice paradigm in adult male and female ethanol-preferring AA (Alko, Alcohol), ethanol-avoiding ANA (Alko, Non-Alcohol) and non-preferring Wistar rats. In addition, analyses of immunoreactive Met-enkephalin-Arg6Phe7 (MEAP), dynorphin B (DYNB) and nociceptin/orphanin FQ (N/OFQ) peptide levels were performed after maternal separation as well as after voluntary ethanol drinking.

In male rats, MS15 was related to lower ethanol consumption and these rats preferred lower concentrations, whereas MS360 was associated with an increased risk for higher consumption and/or preference for higher ethanol concentrations. Differences in basal opioid levels were observed in MS15 and MS360 rats. Furthermore, the ethanol-induced effects on opioid peptides in adults were dependent on the early environment. Female rats, on the other hand, were less affected or unaffected by maternal separation both in terms of ethanol consumption and neurobiological effects. Taken together, voluntary ethanol drinking, preference for low or high ethanol concentrations and opioid peptides in brain areas related to reward and reinforcement, motivation and stress were influenced by postnatal maternal separation in a sex dependent manner. The early environment thus had profound impact on the adult brain and the individual propensity for high ethanol drinking. A deranged endogenous opioid system contributed to these effects and may act as a mediator for long-term environmental influence on voluntary ethanol consumption.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 80 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 51
Keyword
Pharmaceutical pharmacology, Maternal separation, Maternal deprivation, Handling, Isolation, Alcohol, Two-bottle model, Four-bottle model, MEAP, Dynorphin B, Nociceptin/orphanin FQ, Radioimmunoassay, Farmaceutisk farmakologi
Identifiers
urn:nbn:se:uu:diva-7776 (URN)978-91-554-6843-9 (ISBN)
Public defence
2007-04-20, Lecture hall B41, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2007-03-30 Created: 2007-03-30 Last updated: 2009-06-02Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Nylander, Ingrid

Search in DiVA

By author/editor
Roman, ErikaNylander, Ingrid
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Alcoholism: Clinical and Experimental Research
Pharmaceutical SciencesMedical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 559 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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