title: Stress-induced anhedonia correlates with lower hippocampal serotonin transporter protein expression.
abstract: The 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.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang 110001, China. matang88@hotmail.com
authors.forename: Man
authors.initials: M
authors.lastname: Tang
authors.forename: Jieyu
authors.initials: J
authors.lastname: Lei
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Guojun
authors.initials: G
authors.lastname: Liu
authors.forename: Shulei
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000704:Analysis of Variance; D059445:Anhedonia / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013223:Statistics as Topic; D013315:Stress, Psychological / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013395:Sucrose