• Man Tang, Jieyu Lei, Xiao Sun, Guojun Liu, and Shulei Zhao.
• Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang 110001, China. matang88@hotmail.com
• Brain Res. 2013 Jun 4; 1513: 127-34.

AbstractThe serotonin transporter (5-HTT) regulates the extracellular concentration of serotonin, influencing neurotransmission. Evidence suggests that 5-HTT is altered during depression, but the precise changes in 5-HTT expression in the pathogenesis and treatment of depression are not clear. We investigated the protein expression of hippocampal 5-HTT in CD-1 mice exposed to unpredictable chronic mild stress for 10 continuous weeks. Following 6 weeks of the stress procedure, the mice were separated into anhedonic and non-anhedonic groups, which were then treated with fluoxetine (FLX, 10mg/kg/day, i.p.) for 4 weeks. Behavioral state and therapeutic efficacy of the drug treatment were assessed using sucrose preference, physical state of the coat and body weight. Our results show that changes in hippocampal 5-HTT protein expression correlated with stress-induced behavioral states. Decreases in 5-HTT expression were associated with the stress-induced anhedonic state, whereas increases were associated with the stress-induced non-anhedonic state. Following FLX treatment, the changes in 5-HTT expression were reversed in a subpopulation of anhedonic mice, i.e., the treatment-responsive anhedonic mice. The treatment did not alter the changes in the treatment-resistant anhedonic mice or in the non-anhedonic mice. The data indicate that down-regulation of hippocampal 5-HTT protein expression is a signature change associated with anhedonia, a key endophenotype of clinical depression. Differential changes in 5-HTT expression may contribute to variations in the susceptibility to anhedonia.Copyright © 2013 Elsevier B.V. All rights reserved.

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