Vmat2 Heterozygous Mutant Mice Display a Depressive-Like Phenotype
| Autor: | Marc G. Caron, Ramona M. Rodriguiz, Jiechun Zhou, Masato Fukui, William C. Wetsel, Lindsey E. Phillips, Sara X. Jiang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Heterozygote Learned helplessness Stimulation Biology Anxiety Neuropsychological Tests Vesicular monoamine transporter 2 Open field Article chemistry.chemical_compound Mice Corticosterone Internal medicine medicine Animals Depressive Disorder Major General Neuroscience Wild type Reserpine Antidepressive Agents Mice Inbred C57BL Disease Models Animal Monoamine neurotransmitter Endocrinology Phenotype chemistry Vesicular Monoamine Transport Proteins Mutation biology.protein medicine.drug |
| Popis: | The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in humans, we investigated whetherVmat2heterozygous (HET) mice present with depressive-like behaviors. The mutants showed locomotor and rearing retardation in the open field and appeared anhedonic to 1 and 1.5% sucrose solutions. Immobility times forVmat2heterozygotes were prolonged in forced swim and imipramine normalized this behavior. HET animals also showed enhanced immobility in tail suspension and this response was alleviated by fluoxetine, reboxetine, and bupropion. Stimulated GTPγS binding indicated that α2-adrenergic receptors in HET hippocampus were more sensitive to UK 14,304 (5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine) stimulation than in wild type (WT) mice. In learned helplessness, mice were exposed to a shuttle box for 4 d or were given inescapable foot-shocks for the same time period. On day 5, all animals were tested in shock escape. Failure rates and the latency to escape were similar for WT and HET mice that were only pre-exposed to the test apparatus. In foot-shock groups, learned helplessness was more robust in heterozygotes than in WT controls. Basal secretion of serum corticosterone was not distinguished by genotype; however, corticosterone levels in mutants were more responsive to stress. Anxiety-like responses of WT and HET animals in the open field, light-dark exploration, zero maze, and novelty-suppressed feeding tests were indistinguishable. Collectively, these findings suggest thatVmat2heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior. |
| Databáze: | OpenAIRE |
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