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
Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Show others and affiliations
2010 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, 49-55 p.Article in journal (Refereed) Published
Abstract [en]

Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.

Place, publisher, year, edition, pages
2010. Vol. 115, no 1, 49-55 p.
Keyword [en]
Aggressiveness, alchol sensitivity, MAO-B, platelet, rhesus macaque
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-136945DOI: 10.3109/03009731003605813ISI: 000275061700007PubMedID: 20187848OAI: oai:DiVA.org:uu-136945DiVA: diva2:377847
Available from: 2010-12-15 Created: 2010-12-14 Last updated: 2017-12-11Bibliographically approved
In thesis
1. The Relation between Serotonergic Biomarkers and Behaviour: – studies on human primates, non-human primates and transgenic mice
Open this publication in new window or tab >>The Relation between Serotonergic Biomarkers and Behaviour: – studies on human primates, non-human primates and transgenic mice
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rationale: The serotonergic system is involved in the modulation of emotion and plays an important role for personality and vulnerability for psychiatric disorders. In the papers included in this thesis, we investigate three biological factors that have been studied in relation to psychiatric symptoms: Platelet monoamine oxidase B (MAO-B) activity, and variations in the MAO-A and the serotonin transporter (5HTT) genes. We also study intensity dependent auditory evoked potentials (IAEP) as an intermediate phenotype for serotonergic capacity. Platelet MAO-B has been shown to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores of sensation seeking, monotony avoidance, and impulsiveness, as well as for susceptibility for alcoholism. Functional polymorphisms in the promoter of the genes encoding MAO-A and the serotonin transporter result in high- or low- activity alleles that have been associated with numerous psychiatric symptoms. One hypothesis for the shaping of personality is that these genotype variants have prenatal effects on the wiring of the brain. Thus, exploring how the development of the brain is affected by different prenatal serotonin levels is relevant in this context.

Observations: (i) Platelet MAOB activity was associated with monoamine metabolites in cerebrospinal fluid from cisterna magna in monkeys, as well as with voluntary alcohol intake, alcohol-induced aggression, and alcohol sensitivity. (ii) The long 5HTTLPR allele was associated with increased IAEP. (iii) The functional MAOA and 5HTT polymorphisms were associated with symptoms of ADHD-related traits in a population based sample of Swedish adolescents. Associations of these candidate genes with ADHD scores were strenghtened when the platelet MAOB activity was combined with genotype. (iv) Our pilot data showed that treatment of pregnant mice with 5HTT blocking antidepressives resulted in more serotonergic cellbodies in lateral wings of dorsal raphe in the offspring, when compared to saline treatment.

Conclusions: Our studies support the notion that platelet MAOB activity and IAEP are endophenotypes for monoaminergic capacity and related behaviours. The functional candidate polymorphisms in MAOA and 5HTT were linked to behaviour, however, the cause-relationship is unclear and the explanation for the associations need to be further investigated, possibly with focus on prenatal effects of the polymorphisms.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 676
Keyword
Serotonin, MAO-A, 5-HTT, MAO-B, alcohol, ADHD
National Category
Medical and Health Sciences
Research subject
Medicine; Neuroscience
Identifiers
urn:nbn:se:uu:diva-151870 (URN)978-91-554-8091-2 (ISBN)
Public defence
2011-06-11, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-05-20 Created: 2011-04-18 Last updated: 2011-07-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedThe article on UJMS

Authority records BETA

Wargelius, Hanna-Linn

Search in DiVA

By author/editor
Wargelius, Hanna-Linn
By organisation
Department of Neuroscience
In the same journal
Upsala Journal of Medical Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 376 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