PMID- 12784114 OWN - NLM STAT- MEDLINE DCOM- 20030912 LR - 20150311 IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 28 IP - 8 DP - 2003 Aug TI - Reduced behavioral effects of cocaine in heterozygous brain-derived neurotrophic factor (BDNF) knockout mice. PG - 1485-90 AB - Brain-derived neurotrophic factor (BDNF) affects the development of brain neurotransmitter systems, including dopamine and serotonin systems that are important for cocaine's rewarding and locomotor stimulatory properties. Human genomic markers within or near the BDNF locus have been linked to or associated with substance abuse. Post-mortem human brain specimens reveal individual differences in the levels of BDNF mRNA and in mRNA splicing patterns. To assess the effects of lifelong alterations in the levels of BDNF expression on a measure of psychostimulant reward, we have compared locomotor stimulant and rewarding effects of cocaine in heterozygous BDNF knockout mice with effects in their wild-type littermates. Heterozygous BDNF knockout mice displayed less locomotion during habituation and less locomotion after cocaine injections. Cocaine-conditioned place preferences were reduced in the BDNF heterozygotes. These mice displayed no significant difference from saline control values at a dose of 10 mg/kg s.c. cocaine, although they exhibited cocaine-induced preference at a 20 mg/kg dose. These data confirm important roles for BDNF in psychostimulant actions, presumably via neurotrophic effects on dopamine and serotonin systems. Furthermore, these data support suggestions that differences in human BDNF expression may underlie associations between markers near the human BDNF gene locus and drug addiction. FAU - Hall, F Scott AU - Hall FS AD - Molecular Neurobiology Branch, National Institute on Drug Abuse-IRP, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. shall@intra.nida.nih.gov FAU - Drgonova, Jana AU - Drgonova J FAU - Goeb, Michelle AU - Goeb M FAU - Uhl, George R AU - Uhl GR LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030430 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Brain-Derived Neurotrophic Factor) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*deficiency/genetics MH - Cocaine/*pharmacology MH - Dose-Response Relationship, Drug MH - Mice MH - Mice, Knockout MH - Motor Activity/*drug effects/*physiology EDAT- 2003/06/05 05:00 MHDA- 2003/09/13 05:00 CRDT- 2003/06/05 05:00 PHST- 2003/06/05 05:00 [pubmed] PHST- 2003/09/13 05:00 [medline] PHST- 2003/06/05 05:00 [entrez] AID - 1300192 [pii] AID - 10.1038/sj.npp.1300192 [doi] PST - ppublish SO - Neuropsychopharmacology. 2003 Aug;28(8):1485-90. doi: 10.1038/sj.npp.1300192. Epub 2003 Apr 30.