14 research outputs found
Physiologically Relevant Changes in Serotonin Resolved by Fast Microdialysis
Online
microdialysis is a sampling and detection method that enables continuous
interrogation of extracellular molecules in freely moving subjects
under behaviorally relevant conditions. A majority of recent publications
using brain microdialysis in rodents report sample collection times
of 20–30 min. These long sampling times are due, in part, to
limitations in the detection sensitivity of high performance liquid
chromatography (HPLC). By optimizing separation and detection conditions,
we decreased the retention time of serotonin to 2.5 min and the detection
threshold to 0.8 fmol. Sampling times were consequently reduced from
20 to 3 min per sample for online detection of serotonin (and dopamine)
in brain dialysates using a commercial HPLC system. We developed a
strategy to collect and to analyze dialysate samples continuously
from two animals in tandem using the same instrument. Improvements
in temporal resolution enabled elucidation of rapid changes in extracellular
serotonin levels associated with mild stress and circadian rhythms.
These dynamics would be difficult or impossible to differentiate using
conventional microdialysis sampling rates
Small-Molecule Arrays for Sorting G‑Protein-Coupled Receptors
Precise
self-assembled monolayer chemistries and microfluidic technology
are combined to create small-molecule biorecognition arrays. Small-molecule
neurotransmitters or precursors are spatially encoded on monolayer-modified
substrates. This platform enables multiplexed screening of G-protein-coupled
receptors (GPCRs) from complex media via protein–ligand interactions.
Preserving access to all epitopes of small molecules
is critical for GPCR recognition. The ability to address multiple
small molecules on solid substrates and to sort protein mixtures based
on specific affinities is a critical step in creating biochips for
proteomic applications
Perinatal vs Genetic Programming of Serotonin States Associated with Anxiety
Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior