PMID- 17161541 OWN - NLM STAT- MEDLINE DCOM- 20070521 LR - 20240312 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 144 IP - 4 DP - 2007 Feb 23 TI - Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus. PG - 1193-208 AB - Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against stress-induced reductions of hippocampal BDNF protein. The observed prevention of stress-induced deceases in BDNF, however, occurred in a time course inconsistent with the prevention of learned helplessness by wheel running, which is evident following 6 weeks, but not 3 weeks, of wheel running. BDNF suppression in physically active rats was produced by administering a single injection of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg) just prior to stress. Despite reduced levels of hippocampal BDNF mRNA following stress, physically active rats given the combination of fluoxetine and stress remained resistant against learned helplessness. Sedentary rats given both fluoxetine and stress still demonstrated typical learned helplessness behaviors. Fluoxetine by itself reduced BDNF mRNA in sedentary rats only, but did not affect freezing or escape learning 24 h later. Finally, bilateral injections of BDNF (1 mug) into the dentate gyrus prior to stress prevented stress-induced reductions of hippocampal BDNF but did not prevent learned helplessness in sedentary rats. These data indicate that learned helplessness behaviors are independent of the presence or absence of hippocampal BDNF because blocking inescapable stress-induced BDNF suppression does not always prevent learned helplessness, and learned helplessness does not always occur in the presence of reduced BDNF. Results also suggest that the prevention of stress-induced hippocampal BDNF suppression is not necessary for the protective effect of wheel running against learned helplessness. FAU - Greenwood, B N AU - Greenwood BN AD - Department of Integrative Physiology, Center for Neuroscience, University of Colorado, Clare Small Room 104, Campus Box 354, Boulder, CO 80309-0354, USA. Ben.Greenwood@Colorado.edu FAU - Strong, P V AU - Strong PV FAU - Foley, T E AU - Foley TE FAU - Thompson, R S AU - Thompson RS FAU - Fleshner, M AU - Fleshner M LA - eng GR - R01 MH068283/MH/NIMH NIH HHS/United States GR - MH-068283/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061208 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Antidepressive Agents, Second-Generation) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 01K63SUP8D (Fluoxetine) RN - 333DO1RDJY (Serotonin) SB - IM MH - Animals MH - Antidepressive Agents, Second-Generation/pharmacology MH - Anxiety Disorders/metabolism/physiopathology MH - Avoidance Learning/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Depressive Disorder/metabolism/physiopathology MH - Down-Regulation/drug effects/physiology MH - Fear/drug effects/physiology MH - Fluoxetine/pharmacology MH - *Helplessness, Learned MH - Hippocampus/drug effects/*metabolism MH - Male MH - Motor Activity/drug effects/physiology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Inbred F344 MH - Serotonin/metabolism MH - Stress, Psychological/*metabolism/physiopathology PMC - PMC1847581 MID - NIHMS18228 EDAT- 2006/12/13 09:00 MHDA- 2007/05/22 09:00 PMCR- 2008/02/23 CRDT- 2006/12/13 09:00 PHST- 2006/07/11 00:00 [received] PHST- 2006/11/04 00:00 [revised] PHST- 2006/11/06 00:00 [accepted] PHST- 2006/12/13 09:00 [pubmed] PHST- 2007/05/22 09:00 [medline] PHST- 2006/12/13 09:00 [entrez] PHST- 2008/02/23 00:00 [pmc-release] AID - S0306-4522(06)01524-7 [pii] AID - 10.1016/j.neuroscience.2006.11.007 [doi] PST - ppublish SO - Neuroscience. 2007 Feb 23;144(4):1193-208. doi: 10.1016/j.neuroscience.2006.11.007. Epub 2006 Dec 8.