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BDNF-TrkB controls cocaine-induced dendritic spines in rodent nucleus accumbens dissociated from increases in addictive behaviors.
Anderson, Ethan M; Wissman, Anne Marie; Chemplanikal, Joyce; Buzin, Nicole; Guzman, Daniel; Larson, Erin B; Neve, Rachael L; Nestler, Eric J; Cowan, Christopher W; Self, David W.
Affiliation
  • Anderson EM; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
  • Wissman AM; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
  • Chemplanikal J; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
  • Buzin N; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
  • Guzman D; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
  • Larson EB; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
  • Neve RL; Viral Gene Transfer Core, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Nestler EJ; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
  • Cowan CW; Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425.
  • Self DW; Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390; david.self@utsouthwestern.edu.
Proc Natl Acad Sci U S A ; 114(35): 9469-9474, 2017 08 29.
Article in En | MEDLINE | ID: mdl-28808012
Chronic cocaine use is associated with prominent morphological changes in nucleus accumbens shell (NACsh) neurons, including increases in dendritic spine density along with enhanced motivation for cocaine, but a functional relationship between these morphological and behavioral phenomena has not been shown. Here we show that brain-derived neurotrophic factor (BDNF) signaling through tyrosine kinase B (TrkB) receptors in NACsh neurons is necessary for cocaine-induced dendritic spine formation by using either localized TrkB knockout or viral-mediated expression of a dominant negative, kinase-dead TrkB mutant. Interestingly, augmenting wild-type TrkB expression after chronic cocaine self-administration reverses the sustained increase in dendritic spine density, an effect mediated by TrkB signaling pathways that converge on extracellular regulated kinase. Loss of TrkB function after cocaine self-administration, however, leaves spine density intact but markedly enhances the motivation for cocaine, an effect mediated by specific loss of TrkB signaling through phospholipase Cgamma1 (PLCγ1). Conversely, overexpression of PLCγ1 both reduces the motivation for cocaine and reverses dendritic spine density, suggesting a potential target for the treatment of addiction in chronic users. Together, these findings indicate that BDNF-TrkB signaling both mediates and reverses cocaine-induced increases in dendritic spine density in NACsh neurons, and these morphological changes are entirely dissociable from changes in addictive behavior.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cocaine / Brain-Derived Neurotrophic Factor / Cocaine-Related Disorders / Receptor, trkB / Dendritic Spines / Nucleus Accumbens Limits: Animals / Humans / Male Language: En Journal: Proc Natl Acad Sci U S A Year: 2017 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cocaine / Brain-Derived Neurotrophic Factor / Cocaine-Related Disorders / Receptor, trkB / Dendritic Spines / Nucleus Accumbens Limits: Animals / Humans / Male Language: En Journal: Proc Natl Acad Sci U S A Year: 2017 Document type: Article Country of publication: United States