Open AccessPotentiated Striatal Dopamine Release Leads to Hyperdopaminergia in Female Brain-Derived Neurotrophic Factor Heterozygous Mice
Author(s) -
Johnna A. Birbeck,
Madiha Khalid,
Tiffany A. Mathews
Publication year - 2014
Publication title -
acs chemical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/cn400157b
Subject(s) - dopamine , microdialysis , endocrinology , medicine , dopaminergic , brain derived neurotrophic factor , striatum , neurotrophic factors , catecholamine , neurotransmitter , chemistry , biology , central nervous system , receptor
The goal of this study was to determine whether a reduction in brain-derived neurotrophic factor (BDNF) levels in female mice leads to dopaminergic system dysregulation. Through a series of in vivo brain microdialysis and slice voltammetry experiments, we discerned that female BDNF heterozygous (BDNF(+/-)) mice are hyperdopaminergic, similar to their male BDNF(+/-) counterparts. Zero-net flux microdialysis results showed that female BDNF(+/-) mice had increased striatal extracellular dopamine levels, while stimulated regional release by high potassium concentrations potentiated dopamine release through vesicular-mediated depolarization. Using the complementary technique of fast scan cyclic voltammetry, electrical stimulation evoked greater dopamine release in the female BDNF(+/-) mice, whereas dopamine uptake remained unchanged relative to that of female wildtype mice. Following psychostimulant methamphetamine administration, female BDNF(+/-) mice showed potentiated dopamine release compared to their wildtype counterparts. Taken together, these dopamine release impairments in female mice appear to result in a hyperdopaminergic phenotype without concomitant alterations in dopamine uptake.