Potentiated Striatal Dopamine Release Leads to Hyperdopaminergiain Female Brain-Derived Neurotrophic Factor Heterozygous Mice

摘要

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 withoutconcomitant alterations in dopamine uptake.