title: Brain-derived neurotrophic factor rapidly increases AMPA receptor surface expression in rat nucleus accumbens.
abstract: In the rodent nucleus accumbens (NAc), cocaine elevates levels of brain-derived neurotrophic factor (BDNF). Conversely, BDNF can augment cocaine-related behavioral responses. The latter could reflect enhancement of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) transmission, because AMPARs in the NAc mediate some cocaine-induced behaviors. Furthermore, in vitro studies in other cell types show that BDNF can promote AMPAR synaptic delivery. In this study, we investigated whether BDNF similarly promotes AMPAR trafficking in the adult rat NAc. After unilateral intracranial injection of BDNF into NAc core or shell, rats were killed at post-injection times ranging from 30 min to 3 days. NAc core or shell tissue from both injected and non-injected hemispheres was analysed by Western blotting. A protein cross-linking assay was used to measure AMPAR surface expression. Assessment of tropomyosin receptor kinase B signaling demonstrated that injected BDNF was biologically active. BDNF injection into NAc core, but not NAc shell, led to a protein synthesis- and extracellular signal-regulated kinase-dependent increase in cell surface GluA1 and a trend towards increased total GluA1. This was detected 30 min post-injection but not at longer time-points. GluA2 and GluA3 were unaffected, suggesting an effect of BDNF on homomeric GluA1 Ca(2+) -permeable AMPARs. These results demonstrate that exogenous BDNF rapidly increases AMPAR surface expression in the rat NAc core, raising the possibility of a relationship between increases in endogenous BDNF levels and alterations in AMPAR transmission observed in the NAc of cocaine-experienced rats.
authors.affiliation: Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064-3095, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Marina E
authors.initials: ME
authors.lastname: Wolf
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020033:Protein Isoforms; D021122:Protein Subunits; D018091:Receptors, AMPA; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases