Mice overexpressing the 5-hydroxytryptamine transporter show no alterations in feeding behaviour and increased non-feeding responses to fenfluramine.
BACKGROUND
The 5-HT transporter (5-HTT) is implicated in the regulation of appetite. Expression of the 5-HTT varies in the human population, and this variation may determine both individual differences in feeding and abnormal feeding behaviours such as eating disorders.


OBJECTIVE
The effects of 5-HTT expression on feeding and satiety were examined in a transgenic mouse model of 5-HTT overexpression.


METHODS
We measured free-feeding food intake and observed the behavioural satiety sequence (BSS) after food deprivation in mice at baseline and after administration of the anorectic drug fenfluramine.


RESULTS
5-HTT overexpressing mice were both lighter and shorter than their wildtype littermates. Despite this size difference, food intake by transgenic and wildtype mice did not differ. There was no effect of genotype on the BSS or on food intake during the test at baseline. Increasing doses of fenfluramine reduced food intake in a similar manner in both transgenic and wildtype mice. After 0.3 and 1 mg/kg fenfluramine, the temporal pattern of the BSS was the same for both groups, whereas 3 and 10 mg/kg fenfluramine disrupted the BSS. In transgenic mice, this disruption was evident at the 3 mg/kg dose, while in wildtypes, it emerged only at the 10-mg/kg dose.


CONCLUSIONS
These data suggest that overexpression of the 5-HTT does not lead to alterations in feeding or satiety in food-deprived mice but does increase the occurrence of other non-feeding behaviours in response to the 5-HT releasing agent fenfluramine.
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. abbie.pringle@psy.ox.ac.uk
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Pringle
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Jennings
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Bannerman
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Higgs
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D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012528:Satiety Response / Q000187:drug effects; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*
D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D005277:Fenfluramine