Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice.

Abstract

BACKGROUND As a key regulator of serotonergic activity and target of many antidepressant treatments, the serotonin transporter (SERT) represents a potential mediator of anxiety- and depression-related behaviors. Using mice lacking the SERT (SERT KO), we examined the role of SERT function in anxiety- and depression-related behaviors and serotonergic neuron function. METHODS Serotonin transporter knockout mice were evaluated in paradigms designed to assess anxiety-, depression-, and stress-related behaviors. Dorsal raphe nucleus (DRN) function was assessed by quantitative serotonergic cell counting and extracellular electrical recording of neuronal firing properties. RESULTS Serotonin transporter knockout mice showed an increase in latency to feed in a novel situation, more immobility in a forced swim, increased escape latency in a shock escape paradigm, and decreased immobility in tail suspension. No differences in anxiety-related behaviors were seen in the open field and the elevated plus maze. Serotonin transporter knockout mice exhibit a 50% reduction in serotonergic cell number and a fourfold decrease in firing rate in the DRN. CONCLUSIONS Developmental loss of SERT produces altered behaviors in models of depression that are generally opposite to those produced by antidepressant treatment. The reduced serotonergic cell number and firing rate in the DRN of adult SERT KO mice suggest a mechanism for these altered behaviors.

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@article{Lira2003AlteredDB, title={Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice.}, author={Alena Lira and Mingming Zhou and Nathalie Castanon and Mark S. Ansorge and Joshua Gordon and Jasmine H Francis and Maria Bradley-Moore and Josko Lira and Mark Underwood and Victoria Arango and Hank F. Kung and Myron A. Hofer and Ren{\'e} Hen and Jay A Gingrich}, journal={Biological psychiatry}, year={2003}, volume={54 10}, pages={960-71} }