PMID- 11173088 OWN - NLM STAT- MEDLINE DCOM- 20010531 LR - 20190826 IS - 0166-4328 (Print) IS - 0166-4328 (Linking) VI - 120 IP - 1 DP - 2001 Apr 8 TI - Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. PG - 87-95 AB - The mechanism of antidepressant action, at the cellular level, is not clearly understood. It has been reported that chronic antidepressant treatment leads to an up-regulation of brain-derived neurotrophic factor (BDNF) mRNA levels in the hippocampus, and that physical activity (voluntary running) enhances this effect. We wished to investigate whether BDNF expression brought about by these interventions may overcome deficits caused by acute stress, and might impact behavior in an animal model. In this report, we have tested the hypothesis that the combination of the antidepressant, tranylcypromine, and physical exercise could lead to decreased neurotrophin deficits and enhanced swimming time in animals that have been forced to swim in an inescapable water tank. Rats were either treated with tranylcypromine, engaged in voluntary running, or both for one week. After these treatments, the animals underwent a two-day forced swimming procedure. BDNF mRNA levels were significantly depressed in untreated animals subjected to forced swimming. Animals that either underwent prior activity or received antidepressant showed BDNF mRNA levels restored to baseline. Animals receiving the combined intervention showed an increase in hippocampal BDNF mRNA well above baseline. Swimming time during a five-minute test was significantly enhanced in animals receiving the combined intervention over untreated animals. Swimming time was not significantly enhanced over that of animals receiving antidepressant alone, however. Enhanced swimming time correlated with increased levels of BDNF mRNA in one hippocampal sub-region (CA4-hilus). These results suggest that the combination of exercise and antidepressant treatment may have significant neurochemical, and possibly behavioral, effects. In addition, these results support the possibility that the enhancement of BDNF expression may be an important element in the clinical response to antidepressant treatment. The induction of BDNF expression by activity/pharmacological treatment combinations could represent an important intervention for further study, to potentially improve depression treatment and management. FAU - Russo-Neustadt, A AU - Russo-Neustadt A AD - Department of Biology and Microbiology, California State University, 5151 State University Drive, Los Angeles, CA 90032, USA. arusson@calstatela.edu FAU - Ha, T AU - Ha T FAU - Ramirez, R AU - Ramirez R FAU - Kesslak, J P AU - Kesslak JP LA - eng GR - AG-13880/AG/NIA NIH HHS/United States GR - MH-59776/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 3E3V44J4Z9 (Tranylcypromine) SB - IM MH - Animals MH - Antidepressive Agents/*pharmacology MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/drug effects/genetics/*metabolism MH - Combined Modality Therapy MH - Depression/drug therapy/*therapy MH - Disease Models, Animal MH - Hippocampus/*metabolism MH - In Situ Hybridization MH - Male MH - Physical Conditioning, Animal/*methods MH - Physical Exertion/drug effects MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Tranylcypromine/*pharmacology MH - Up-Regulation EDAT- 2001/02/15 11:00 MHDA- 2001/06/02 10:01 CRDT- 2001/02/15 11:00 PHST- 2001/02/15 11:00 [pubmed] PHST- 2001/06/02 10:01 [medline] PHST- 2001/02/15 11:00 [entrez] AID - S0166-4328(00)00364-8 [pii] AID - 10.1016/s0166-4328(00)00364-8 [doi] PST - ppublish SO - Behav Brain Res. 2001 Apr 8;120(1):87-95. doi: 10.1016/s0166-4328(00)00364-8.