PMID- 10611369 OWN - NLM STAT- MEDLINE DCOM- 20000127 LR - 20230331 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 96 IP - 26 DP - 1999 Dec 21 TI - Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. PG - 15239-44 AB - Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, the role of endogenous BDNF in the development and function of these neurons has not been established in vivo because of the early postnatal lethality of BDNF null mice. In the present study, we use heterozygous BDNF(+/-) mice that have a normal life span and show that these animals develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood; these behavioral abnormalities are known to correlate with 5-HT dysfunction. Forebrain 5-HT levels and fiber density in BDNF(+/-) mice are normal at an early age but undergo premature age-associated decrements. However, young adult BDNF(+/-) mice show a blunted c-fos induction by the specific serotonin releaser-uptake inhibitor dexfenfluramine and alterations in the expression of several 5-HT receptors in the cortex, hippocampus, and hypothalamus. The heightened aggressiveness can be ameliorated by the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells. Therefore, BDNF(+/-) mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons. FAU - Lyons, W E AU - Lyons WE AD - Neural Development Group, Advanced BioScience Laboratories/Basic Research Program, National Cancer Institute/Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. FAU - Mamounas, L A AU - Mamounas LA FAU - Ricaurte, G A AU - Ricaurte GA FAU - Coppola, V AU - Coppola V FAU - Reid, S W AU - Reid SW FAU - Bora, S H AU - Bora SH FAU - Wihler, C AU - Wihler C FAU - Koliatsos, V E AU - Koliatsos VE FAU - Tessarollo, L AU - Tessarollo L LA - eng GR - F32 MH085433/MH/NIMH NIH HHS/United States GR - F32 NS010580/NS/NINDS NIH HHS/United States GR - NS 10580/NS/NINDS NIH HHS/United States GR - R29MH85433/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 - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 333DO1RDJY (Serotonin) RN - E35R3G56OV (Dexfenfluramine) SB - IM MH - *Aggression MH - Animals MH - Behavior, Animal MH - Brain/*physiopathology MH - Brain-Derived Neurotrophic Factor/*deficiency/genetics MH - Dexfenfluramine/pharmacology MH - Female MH - Heterozygote MH - *Hyperphagia MH - Male MH - Mice MH - Mice, Mutant Strains MH - Proto-Oncogene Proteins c-fos/biosynthesis MH - Serotonin/*metabolism PMC - PMC24804 EDAT- 1999/12/28 00:00 MHDA- 1999/12/28 00:01 PMCR- 2000/06/21 CRDT- 1999/12/28 00:00 PHST- 1999/12/28 00:00 [pubmed] PHST- 1999/12/28 00:01 [medline] PHST- 1999/12/28 00:00 [entrez] PHST- 2000/06/21 00:00 [pmc-release] AID - 4583 [pii] AID - 10.1073/pnas.96.26.15239 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15239-44. doi: 10.1073/pnas.96.26.15239.