Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels. / Jennings, Katie Ann; Licht, Cecilie Löe; Bruce, Aynsley; Lesch, Klaus-Peter; Knudsen, Gitte Moos; Sharp, Trevor.
In: International Journal of Neuropsychopharmacology, Vol. 15, No. 8, 2012, p. 1099-1107.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels
AU - Jennings, Katie Ann
AU - Licht, Cecilie Löe
AU - Bruce, Aynsley
AU - Lesch, Klaus-Peter
AU - Knudsen, Gitte Moos
AU - Sharp, Trevor
PY - 2012
Y1 - 2012
N2 - Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for psychiatric disorder and has been linked to changes in the expression of certain 5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT expression on 5-HT4 receptor levels in both 5-HTT knockout (KO) and overexpressing (OE) mice using autoradiography with the selective 5-HT4 receptor radioligand, [3H]SB207145. Compared to wild-type (5-HTT+/+) controls, homozygous 5-HTT KO mice (5-HTT-/-) had reduced 5-HT4 receptor binding site density in all brain regions examined (35-65% of 5-HTT+/+). In contrast, the density of 5-HT4 receptor binding sites was not significantly different between heterozygous 5-HTT KO mice (5-HTT-/+) and 5-HTT+/+ mice. The 5-HT synthesis inhibitor p-chlorophenylalanine (250 mg/kg twice daily for 3 d) abolished the difference in 5-HT4 binding between 5-HTT-/- and 5-HTT+/+ mice in all brain regions. Compared to wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT4 binding density across all brain regions, except amygdala (118-164% of WT) and this difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20 mg/kg twice daily, 3 d). Together, these findings suggest that variation in 5-HTT expression causes adaptive changes in 5-HT4 receptor levels which are directly linked to alterations in 5-HT availability.
AB - Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for psychiatric disorder and has been linked to changes in the expression of certain 5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT expression on 5-HT4 receptor levels in both 5-HTT knockout (KO) and overexpressing (OE) mice using autoradiography with the selective 5-HT4 receptor radioligand, [3H]SB207145. Compared to wild-type (5-HTT+/+) controls, homozygous 5-HTT KO mice (5-HTT-/-) had reduced 5-HT4 receptor binding site density in all brain regions examined (35-65% of 5-HTT+/+). In contrast, the density of 5-HT4 receptor binding sites was not significantly different between heterozygous 5-HTT KO mice (5-HTT-/+) and 5-HTT+/+ mice. The 5-HT synthesis inhibitor p-chlorophenylalanine (250 mg/kg twice daily for 3 d) abolished the difference in 5-HT4 binding between 5-HTT-/- and 5-HTT+/+ mice in all brain regions. Compared to wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT4 binding density across all brain regions, except amygdala (118-164% of WT) and this difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20 mg/kg twice daily, 3 d). Together, these findings suggest that variation in 5-HTT expression causes adaptive changes in 5-HT4 receptor levels which are directly linked to alterations in 5-HT availability.
U2 - 10.1017/S1461145711001258
DO - 10.1017/S1461145711001258
M3 - Journal article
C2 - 21846421
VL - 15
SP - 1099
EP - 1107
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 8
ER -
ID: 34398475