title: Regular moderate or intense exercise prevents depression-like behavior without change of hippocampal tryptophan content in chronically tryptophan-deficient and stressed mice.
abstract: Regular exercise has an antidepressant effect in human subjects. Studies using animals have suggested that the antidepressant effect of exercise is attributable to an increase of brain 5-hydroxytryptamine (5-HT); however, the precise mechanism underlying the antidepressant action via exercise is unclear. In contrast, the effect of 5-HT on antidepressant activity has not been clarified, in part because the therapeutic response to antidepressant drugs has a time lag in spite of the rapid increase of brain 5-HT upon administration of these drugs. This study was designed to investigate the contribution of brain 5-HT to the antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and stressed using chronic unpredictable stress (CUS) for 4 weeks with or without the performance of either moderate or intense exercise on a treadmill 3 days per week. The findings demonstrated that the onset of depression-like behavior is attributable not to chronic reduction of 5-HT but to chronic stress. Regular exercise, whether moderate or intense, prevents depression-like behavior with an improvement of adult hippocampal cell proliferation and survival and without the recovery of 5-HT. Concomitantly, the mice that exercised showed increased hippocampal noradrenaline. Regular exercise prevents the impairment of not long-term memory but short-term memory in a 5-HT-reduced state. Together, these findings suggest that: (1) chronic reduction of brain 5-HT may not contribute to the onset of depression-like behavior; (2) regular exercise, whether moderate or intense, prevents the onset of chronic stress-induced depression-like behavior independent of brain 5-HT and dependent on brain adrenaline; and (3) regular exercise prevents chronic tryptophan reduction-induced impairment of not long-term but short-term memory.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Nakahara-ku, Kawasaki, Japan.
authors.forename: Hosung
authors.initials: H
authors.lastname: Lee
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohno
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
authors.forename: Toshio
authors.initials: T
authors.lastname: Mikami
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001923:Brain Chemistry; D049109:Cell Proliferation; D003863:Depression / Q000517:prevention & control* / Q000523:psychology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013315:Stress, Psychological; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D012701:Serotonin; D014364:Tryptophan; D009638:Norepinephrine