TY - JOUR
T1 - Cerebral metabolic responses to 5-HT2A/C receptor activation in mice with genetically modified serotonin transporter (SERT) expression
AU - Dawson, Neil
AU - Ferrington, Linda
AU - Lesch, Klaus-Peter
AU - Kelly, Paul A. T.
PY - 2011/1
Y1 - 2011/1
N2 - Variation in the human serotonin transporter gene (hSERT; 5-HTT) resulting in a life-long alteration in SERT function influences anxiety and the risk of developing affective disorders. The mechanisms underlying the influence of the hSERT gene on these phenotypes remain unclear but may involve altered 5-HT receptor function. Here we characterise the cerebral metabolic response to 5-HT2A/C receptor activation in two transgenic mouse models of altered SERT function, SERT knock-out (SERT KO) and hSERT over-expressing (hSERT OE) mice, to test the hypothesis that genetically mediated variability in SERT expression alters 5-HT2A/C function. We found that a constitutive increase in SERT expression (hSERT OE) enhanced, whereas a constitutive decrease in SERT expression (SERT KO) attenuated, 5-HT2A/C function. Therefore, altered 5-HT2A/C receptor functioning in response to hSERT gene variation may contribute to its influence on affective phenotypes. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.
AB - Variation in the human serotonin transporter gene (hSERT; 5-HTT) resulting in a life-long alteration in SERT function influences anxiety and the risk of developing affective disorders. The mechanisms underlying the influence of the hSERT gene on these phenotypes remain unclear but may involve altered 5-HT receptor function. Here we characterise the cerebral metabolic response to 5-HT2A/C receptor activation in two transgenic mouse models of altered SERT function, SERT knock-out (SERT KO) and hSERT over-expressing (hSERT OE) mice, to test the hypothesis that genetically mediated variability in SERT expression alters 5-HT2A/C function. We found that a constitutive increase in SERT expression (hSERT OE) enhanced, whereas a constitutive decrease in SERT expression (SERT KO) attenuated, 5-HT2A/C function. Therefore, altered 5-HT2A/C receptor functioning in response to hSERT gene variation may contribute to its influence on affective phenotypes. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.
UR - http://www.scopus.com/inward/record.url?scp=78650678064&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2010.10.006
DO - 10.1016/j.euroneuro.2010.10.006
M3 - Article
SN - 0924-977X
VL - 21
SP - 117
EP - 128
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 1
ER -