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Increased GABAA receptor binding in amygdala after prenatal administration of valproic acid to rats

Published online by Cambridge University Press:  12 December 2016

Freja Bertelsen ,
Arne Møller ,
Davide Folloni ,
Kim Ryun Drasbek ,
Jørgen Scheel-Krüger  and
Anne M. Landau
Freja Bertelsen
Affiliation:
Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Nuclear Medicine and PET Centre, Aarhus University and Hospital, Aarhus, Denmark
Arne Møller
Affiliation:
Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Nuclear Medicine and PET Centre, Aarhus University and Hospital, Aarhus, Denmark
Davide Folloni
Affiliation:
Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Experimental Psychology, University of Oxford, Oxford, UK
Kim Ryun Drasbek
Affiliation:
Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
Jørgen Scheel-Krüger
Affiliation:
Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
Anne M. Landau*
Affiliation:
Department of Nuclear Medicine and PET Centre, Aarhus University and Hospital, Aarhus, Denmark Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark
*
Anne M. Landau, Department of Nuclear Medicine and PET Centre, Nørrebrogade 44, Building 10G, 8000 Aarhus, Denmark. Tel: +45 7846 3029; Fax: +45 7846 1662; E-mail: [email protected]
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Abstract

Objective

Prenatal exposure to valproic acid (VPA) enhances the risk for later development of autism spectrum disorders (ASD). An altered gamma-aminobutyric acid (GABA) system may be a key factor in ASD. Here we investigated possible changes in the GABA system in rats exposed to a low dose of prenatal VPA.

Method

We performed autoradiography with [3H]muscimol, (a GABAA receptor agonist), and [11C]Ro15-4513 (a partial agonist of the GABAA α1+5 receptor subtypes), in brain sections containing amygdala, thalamus and hippocampus of rats treated prenatally with 20 mg/kg VPA or saline from the 12th day of gestation.

Result

Prenatal VPA significantly increased [11C]Ro15-4513 binding in the left amygdala compared with controls (p<0.05). This difference was not observed in the hippocampus, thalamus or right amygdala. No differences were observed in [3H]muscimol binding.

Conclusion

We observed an asymmetric increase in GABAA receptor binding. Disturbances in the GABAA receptor system have also been detected in human autism with [11C]Ro15-4513.

Keywords

[11C]Ro-154513autism spectrum disordersautoradiographyGABAvalproic acid
Type
Short Communications
Information
Acta Neuropsychiatrica , Volume 29 , Issue 5 , October 2017 , pp. 309 - 314
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Copyright
© Scandinavian College of Neuropsychopharmacology 2016 

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