Deep brain stimulation mediates neurotrophin signaling in an animal model of antidepressant resistance

Chronic adrenocorticotropic hormone administration at circadian nadir produces an antidepressant resistance animal model that does not present with an altered plasma corticosterone profile nor changes in hippocampal brain derived neurotrophic factor and its receptor. Acute and chronic infralimbic deep brain stimulation elicited an antidepressant response in this animal model, which appears to be associated with changes in gene and protein expression of key intracellular mediators of neurotrophic factor signaling. Together, these findings stand to make important positive impacts on treatment strategies for one of the most debilitating and prevalent disorders of the modern era and suggest that antidepressant treatment response may involve mechanisms distinct from chronic stress-mediated induction of depression-like behavioral phenotypes

Determination of neurotransmitters and their metabolites using one- and two-dimensional liquid chromatography with acidic potassium permanganate chemiluminescence detection

High-performance liquid chromatography with chemiluminescence detection based on the reaction with acidic potassium permanganate and formaldehyde was explored for the determination of neurotransmitters and their metabolites. The neurotransmitters norepinephrine and dopamine were quantified in the left and right hemispheres of rat hippocampus, nucleus accumbens and prefrontal cortex, and the metabolites vanillylmandelic acid, 3,4-dihydrophenylacetic acid, 5-hydroxyindole-3-acetic acid and homovanillic acid were identified in human urine. Under optimised chemiluminescence reagent conditions, the limits of detection for these analytes ranged from 2.5 × 10−8 to 2.5 × 10−7 M. For the determination of neurotransmitter metabolites in urine, a two-dimensional high-performance liquid chromatography (2D-HPLC) separation operated in heart-cutting mode was developed to overcome the peak capacity limitations of the one-dimensional separation. This approach provided the greater separation power of 2D-HPLC with analysis times comparable to conventional one-dimensional separations