The Department of Biomedicine

BBB seminar: Trevor Sharp

Neurobiological effects of genetic variation in the 5-HT transporter

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Trevor Sharp
Department of Pharmacology, University of Oxford, UK

The serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) plays a key role in regulating transmission at 5 HT synapses in the brain. The human 5-HTT gene has commonly occurring polymorphic variants, some of which have been associated with altered anxiety phenotypes in human volunteers and patient populations. However, it is uncertain whether these genotype-phenotype associations relate to variation in 5-HTT expression. For example, there is no clear agreement from PET studies that 5-HTT polymorphic variants lead to different 5-HTT levels in the brain. This seminar will analyse this issue from the perspective of animal models of 5-HTT variation, including a recently developed mouse genetically engineered to over-express the 5-HTT. The current knowledge of the neurochemical and behavioural phenotypes of the 5-HTT overexpressing mouse will be reviewed. In addition, the phenotypes of the latter mouse will be compared and contrasted with those of the 5-HTT knock-out mouse. Finally, the influence of development and environmental factors on 5-HTT-associated phenotypes in animals and humans will be discussed.

Host: Jan Haavik <jan.haavik@biomed.uib.no>, Department of Biomedicine