| Autor: |
Jennings KA; University Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, UK. katie.jennings@dpag.ox.ac.uk, Licht CL, Bruce A, Lesch KP, Knudsen GM, Sharp T |
| Jazyk: |
angličtina |
| Zdroj: |
The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2012 Sep; Vol. 15 (8), pp. 1099-107. Date of Electronic Publication: 2011 Aug 16. |
| DOI: |
10.1017/S1461145711001258 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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