QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 26, 2007, 27(39):10520-10529; doi:10.1523/JNEUROSCI.4388-06.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fukui, M. Articles by Wetsel, W. C. Search for Related Content PubMed PubMed Citation Articles by Fukui, M. Articles by Wetsel, W. C.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Vmat2 Heterozygous Mutant Mice Display a Depressive-Like Phenotype

Masato Fukui,¹ Ramona M. Rodriguiz,¹ Jiechun Zhou,¹ Sara X. Jiang,¹ Lindsey E. Phillips,¹ Marc G. Caron,² and William C. Wetsel^1,3

¹Department of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, ²Department of Cell Biology, and ³Departments of Cell Biology and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710

Correspondence should be addressed to William C. Wetsel, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 028 CARL Building, Research Drive, Durham, NC 27710. Email: wetse001{at}mc.duke.edu

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 whether Vmat2 heterozygous (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 for Vmat2 heterozygotes 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 GTPS binding indicated that ₂-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 that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

Key words: vesicular monoamine transporter 2; anxiety; locomotion; anhedonia; depressive-like behavior; antidepressant; stress

---

Received Oct. 8, 2006; revised Aug. 14, 2007; accepted Aug. 14, 2007.

Correspondence should be addressed to William C. Wetsel, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 028 CARL Building, Research Drive, Durham, NC 27710. Email: wetse001{at}mc.duke.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help