Stress-induced anhedonia correlates with lower hippocampal serotonin transporter protein expression

• Published in: Brain research 2013-06, Vol.1513, p.127-134
• Main Authors: Tang, Man, Lei, Jieyu, Sun, Xiao, Liu, Guojun, Zhao, Shulei
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Anhedonia; Anhedonia - physiology; Animals; Behavioral psychophysiology; Biological and medical sciences; body weight; Body Weight - drug effects; brain; Disease Models, Animal; drug therapy; Fluoxetine; Fluoxetine - pharmacology; Fluoxetine - therapeutic use; Food Preferences - drug effects; Food Preferences - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hippocampus; Hippocampus - metabolism; Male; Medical sciences; Mice; Neurology; Neuropharmacology; Neurotransmission and behavior; pathogenesis; Pharmacology. Drug treatments; protein synthesis; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; serotonin; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin transporter; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; Statistics as Topic; Stress, Psychological - drug therapy; Stress, Psychological - pathology; Stress, Psychological - physiopathology; sucrose; Sucrose - administration & dosage; Sucrose preference; Time Factors; Unpredictable chronic mild stress
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2013.03.042

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, 10 mg/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.