Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice.
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.
Lira
Alena
A
Division of Developmental Psychobiology, Columbia University, New York, New York 10032, USA.
Zhou
Mingming
M
Castanon
Nathalie
N
Ansorge
Mark S
MS
Gordon
Joshua A
JA
Francis
Jasmine H
JH
Bradley-Moore
Maria
M
Lira
Josko
J
Underwood
Mark D
MD
Arango
Victoria
V
Kung
Hank F
HF
Hofer
Myron A
MA
Hen
René
R
Gingrich
Jay A
JA
D000200:Action Potentials; D000698:Analgesia; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001345:Autoradiography; D001362:Avoidance Learning; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D004307:Dose-Response Relationship, Radiation; D004594:Electrophysiology / Q000379:methods; D004597:Electroshock / Q000379:methods; D004924:Escape Reaction; D005106:Exploratory Behavior; D005247:Feeding Behavior; D005260:Female; D019417:Hindlimb Suspension; D007150:Immunohistochemistry; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D008298:Maleates / Q000493:pharmacokinetics; D018782:Maze Learning; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D011903:Raphe Nuclei / Q000378:metabolism / Q000503:physiopathology*; D011930:Reaction Time; D050486:Serotonin Plasma Membrane Transport Proteins; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology; D013550:Swimming; D013997:Time Factors
D002352:Carrier Proteins; D007456:Iodine Isotopes; D008298:Maleates; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; C465814:dansylaminomethylmaleic anhydride