PMID- 12211082 OWN - NLM STAT- MEDLINE DCOM- 20021119 LR - 20131121 IS - 0887-4476 (Print) IS - 0887-4476 (Linking) VI - 46 IP - 2 DP - 2002 Nov TI - Neutralization of neutrophin-3 in the ventral tegmental area or nucleus accumbens differentially modulates cocaine-induced behavioral plasticity in rats. PG - 57-65 AB - These experiments were designed to assess the influence of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) in the mesoaccumbens dopamine system on the initiation of behavioral sensitization to cocaine. A neutralizing antibody for NT-3, BDNF or their vehicle was administered into the ventral tegmental area (VTA) or nucleus accumbens prior to each of four daily injections of 15 mg/kg cocaine. Behavioral sensitization was operationally defined as a significant increase in the behavioral response to cocaine relative to the first daily injection. Results indicated that the NT-3 antibody had differential effects when administered into the VTA or nucleus accumbens. Intra-VTA microinjection of anti-NT-3 resulted in enhanced sensitization to repeated cocaine injections in that the cocaine-induced behavioral response in the anti-NT-3 group was significantly greater than the vehicle group following the second and third daily injections of cocaine. Administration of anti-NT-3 into the nucleus accumbens increased the behavioral response to cocaine over all 4 days of cocaine administration, with no sensitization of this behavioral response. In contrast, pretreatment with anti-BDNF into the VTA or nucleus accumbens had no influence on the initiation of behavioral sensitization to cocaine. Taken together, these data indicate that neutralization of NT-3 in the VTA enhances cocaine-induced behavioral sensitization, while administration of the NT-3 antibody into the nucleus accumbens increases the hyperactive behavioral response induced by cocaine but impairs the further development of behavioral sensitization. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Freeman, Antoinette Y AU - Freeman AY AD - Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. FAU - Pierce, R Christopher AU - Pierce RC LA - eng GR - R01 DA12171/DA/NIDA 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 - Synapse JT - Synapse (New York, N.Y.) JID - 8806914 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Neurotrophin 3) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Antibodies/administration & dosage/immunology MH - Behavior, Animal/*drug effects MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors MH - Cocaine/*pharmacology MH - Dopamine Uptake Inhibitors/*pharmacology MH - Injections, Intraventricular MH - Male MH - Neurotrophin 3/*antagonists & inhibitors/immunology MH - Nucleus Accumbens/*drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Ventral Tegmental Area/*drug effects/metabolism EDAT- 2002/09/05 10:00 MHDA- 2002/11/26 04:00 CRDT- 2002/09/05 10:00 PHST- 2002/09/05 10:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/09/05 10:00 [entrez] AID - 10.1002/syn.10123 [doi] PST - ppublish SO - Synapse. 2002 Nov;46(2):57-65. doi: 10.1002/syn.10123.