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Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice
Author(s) -
Montañez Sylvia,
Owens W. Anthony,
Gould Georgianna G.,
Murphy Dennis L.,
Daws Lynette C.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01836.x
Subject(s) - fluvoxamine , endocrinology , medicine , heterozygote advantage , serotonin transporter , serotonin , norepinephrine transporter , desipramine , knockout mouse , chemistry , hippocampus , biology , antidepressant , fluoxetine , genotype , biochemistry , receptor , gene
Clearance rates for serotonin (5‐HT) in heterozygote (+/–) and homozygote (–/–) serotonin transporter (5‐HTT) knockout (KO) mice have not been determined in vivo . Moreover, the effect of selective serotonin reuptake inhibitors (SSRIs) on 5‐HT clearance in these mice has not been examined. In this study, the rate of clearance of exogenously applied 5‐HT was measured in the CA3 region of the hippocampus of anesthetized mice using high‐speed chronoamperometry. Compared with wild‐type mice, the maximal rate of 5‐HT clearance from extracellular fluid (ECF) was decreased in heterozygotes and more markedly so in KO mice. Heterozygote mice were more sensitive to the 5‐HT uptake inhibitor, fluvoxamine, resulting in longer clearance times for 5‐HT than in wild‐type mice; as expected, the KO mice were completely unresponsive to fluvoxamine. There were no associated changes in norepinephrine transporter density, nor was there an effect of the norepinephrine uptake inhibitor, desipramine, on 5‐HT clearance in any genotype. Thus, adaptive changes in the norepinephrine transport system do not occur in the CA3 region of hippocampus as a consequence of 5‐HTT KO. These data highlight the potential of the heterozygote 5‐HTT mutant mice to model the dynamic in vivo consequences of the human 5‐HTT polymorphism.