| First Author | Jennings KA | Year | 2012 |
| Journal | Int J Neuropsychopharmacol | Volume | 15 |
| Issue | 8 | Pages | 1099-107 |
| PubMed ID | 21846421 | Mgi Jnum | J:285707 |
| Mgi Id | MGI:6400090 | Doi | 10.1017/S1461145711001258 |
| Citation | Jennings KA, et al. (2012) Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT(4) receptor levels. Int J Neuropsychopharmacol 15(8):1099-107 |
| abstractText | 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-HT(4) receptor levels in both 5-HTT knockout (KO) and overexpressing (OE) mice using autoradiography with the selective 5-HT(4) receptor radioligand, [(3)H]SB207145. Compared to wild-type (5-HTT(+)/(+)) controls, homozygous 5-HTT KO mice (5-HTT(-)/(-)) had reduced 5-HT(4) receptor binding site density in all brain regions examined (35-65% of 5-HTT(+)/(+)). In contrast, the density of 5-HT(4) 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-HT(4) 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-HT(4) 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-HT(4) receptor levels which are directly linked to alterations in 5-HT availability. |
