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Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Neuropharmacology, Addiction & Behaviour)
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, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
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2009 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1305, no Suppl. 1, S37-S49 p.Article in journal (Refereed) Published
Abstract [en]

Early environment is a known determinant for individual differences in vulnerability for adult psychopathology, e.g. ethanol addiction. One underlying mechanism could be dysfunction in serotonergic neurotransmission. This study focused on the methodological considerations regarding an animal model for studying effects of early environment, maternal separation (MS), using two different paradigms. Age- and sex-specific effects on brain stem 5-hydroxytryptamine (5-HT) transporter and receptors were examined. Male and female rat pups were assigned to either litter-wise MS for 15 or 360 minutes (MS15l or MS360l) or individual MS for 15 or 360 minutes (MS15i or MS360i) daily during postnatal days 1-21. Normal animal facility reared rats were used as controls. Analyses were performed in young and adult rats. As compared to the other males, MS15l males had lower 5-HT1A and 5-HT2C receptor mRNA expression at both ages, lower 5-HT2A receptor mRNA when young and lower 5-HTT mRNA expression when adult. In contrast, adult MS15l females had higher 5-HT2C receptor mRNA expression than the other females. The strong impact of MS15l on 5-HT-related genes was either transient or persistent depending on sex and fewer effects on gene expression were observed in females than in males. This study shows the importance of tactile contact for the consequences of short, but not long MS, as evidenced by major differences between MS15l and MS15i. The results suggest that MS15i is less suitable than MS15l to simulate a protective environment in studies of for instance ethanol addiction processes. 

Place, publisher, year, edition, pages
Elsevier , 2009. Vol. 1305, no Suppl. 1, S37-S49 p.
Keyword [en]
Early-life Environment, 5-HT1A receptor, 5-HT2A receptor, 5-HT2C receptor, 5-HT3 receptor, Serotonin
National Category
Medical and Health Sciences
Research subject
Pharmaceutical Pharmacology
Identifiers
URN: urn:nbn:se:uu:diva-108908DOI: 10.1016/j.brainres.2009.08.069ISI: 000273202100006PubMedID: 19728999OAI: oai:DiVA.org:uu-108908DiVA: diva2:241441
Available from: 2009-10-09 Created: 2009-10-02 Last updated: 2011-11-02Bibliographically approved
In thesis
1. Maternal Separation in the Rat: The Short- and Long-term effects of Early-life Experience on Neuropeptides, Monoamines and Voluntary Ethanol Consumption
Open this publication in new window or tab >>Maternal Separation in the Rat: The Short- and Long-term effects of Early-life Experience on Neuropeptides, Monoamines and Voluntary Ethanol Consumption
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Early-life experience has profound effects on the individual’s neurobiology and behaviour later in life. The rodent animal experimental model maternal separation (MS) was used to study this more in detail. The MS model involves short and prolonged postnatal separations simulating an emotionally safe and stressful environment, respectively. The aims of the thesis were to examine the impact of individual MS on ethanol consumption and on brain dopamine and serotonin systems in adult male rats. Furthermore, the influence of separation conditions on the short- and long-term consequences of MS on several neurotransmitter systems was examined.

Rat pups were assigned to either litter-wise MS for 15 or 360 minutes (MS15l or MS360l) or individual MS for 15 or 360 minutes (MS15i or MS360i). Control rats were subjected to conventional animal facility rearing (AFR). Ethanol intake was assessed in a two-bottle free-choice paradigm. Neuropeptides were analyzed with radioimmunoassay, monoamines and metabolites with electrochemical detection and gene expression with qPCR.

Using the MSi paradigm, minor effects on voluntary ethanol consumption were observed. However, the monoaminergic responses elicited by ethanol were dependent on the early-life environment.

Furthermore, short- and long-term consequences of MS on serotonin, opioid, oxytocin and vasopressin systems were studied. Multiple neurobiological measurements in one and the same rat offered a unique possibility to examine the effects of duration (MS15 versus MS360) and condition (l versus i) of MS. Time-, region-, sex- and transmitter-specific effects were observed. More pronounced differences were seen in serotonin measures and oxytocin in young rats. In adults these differences in basal levels were normalized. Opioid peptides differed in stress-related brain areas in young rats and in limbic areas in adults. Rats subjected to the MS15l environment that relates to natural conditions generally exhibited a different neurobiological profile than other groups. AFR rats, i.e. conventional control rats, were more similar to the putative most stressful condition MS360. Taken together, the networks examined in the present thesis are important for the establishment of normal social behaviour and derangements in these systems may result in neurobiological changes leading to the susceptibility for psychopathological conditions later in life.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 87 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 106
Keyword
Early-life stress, Handling, Serotonin, Dopamine, Oxytocin, Vasopressin, Enkephalin, Dynorphin, Two-bottle free choice, Maternal deprivation
National Category
Pharmacology and Toxicology
Research subject
Pharmaceutical Pharmacology
Identifiers
urn:nbn:se:uu:diva-108678 (URN)978-91-554-7615-1 (ISBN)
Public defence
2009-11-07, B41, BMC, Husargatan 3, Uppsala, 09:15 (English)
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Supervisors
Available from: 2009-10-16 Created: 2009-09-25 Last updated: 2011-05-11Bibliographically approved

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