• Alena Lira, Mingming Zhou, Nathalie Castanon, Mark S Ansorge, Joshua A Gordon, Jasmine H Francis, Maria Bradley-Moore, Josko Lira, Mark D Underwood, Victoria Arango, Hank F Kung, Myron A Hofer, René Hen, and Jay A Gingrich.
• Division of Developmental Psychobiology, Columbia University, New York, New York 10032, USA.
• Neuropsychopharmacology. 2003 Nov 15; 54 (10): 960-71.

BackgroundAs 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.MethodsSerotonin 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.ResultsSerotonin 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.ConclusionsDevelopmental 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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