title: Probing the ability of presynaptic tyrosine kinase receptors to regulate striatal dopamine dynamics.
abstract: Brain-derived neurotrophic factor (BDNF) modulates the synaptic transmission of several monoaminergic neuronal systems. Molecular techniques using synapatosomes in previous studies have suggested that BDNF's receptor, tyrosine kinases (Trk), can quickly regulate dopamine release and transporter dynamics. Our main objective in this study is to determine whether slice fast scan cyclic voltammetry can be used to investigate the role of the TrkB receptor on dopamine release and uptake processes in the caudate-putamen. Fast scan cyclic voltammetry measured dopamine release and uptake rates in the presence of BDNF, or its agonist 7,8-dihydroxyflavone, or a TrkB inhibitor K252a. Superfusion of BDNF led to partial recovery of the electrically stimulated dopamine release response in BDNF(+/-) mice which is blunted compared to wildtype mice, with no effect in wildtype mice. Conversely, infusion of 7,8-dihydroxyflavone increased electrically stimulated dopamine release in wildtype mice with no difference in BDNF(+/-) mice. Overall, BDNF and 7,8-dihydroxyflavone had no effect on dopamine uptake rates. Concentrations greater than 3 μM 7,8-dihydroxyflavone affected dopamine uptake rates in BDNF(+/-) mice only. To demonstrate that BDNF and 7,8-dihydroxyflavone modulate dopamine release by activating the TrkB receptor, both genotypes were pretreated with K252a. K252a was able to block BDNF and 7,8-DHF induced increases during stimulated dopamine release in BDNF(+/-) and wildtype mice, respectively. Fast scan cyclic voltammetry demonstrates that acute TrkB activation potentiates dopamine release in both genotypes.
authors: Department of Chemistry, Wayne State University , Detroit, MI 48202, United States.
authors: Aaron K
authors: AK
authors: Apawu
authors: Francis K
authors: FK
authors: Maina
authors: James R
authors: JR
authors: Taylor
authors: Tiffany A
authors: TA
authors: Mathews
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D055664:Electrochemical Techniques; D047309:Flavones / Q000494:pharmacology; D026121:Indole Alkaloids / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000502:physiology; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C485383:6,7-dihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D047309:Flavones; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D020813:Receptor, trkB; D004298:Dopamine
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