Sex- and SERT-Mediated Differences in Stimulated Serotonin Revealed by Fast Microdialysis

Abstract

In vivo microdialysis is widely used to investigate how neurotransmitter levels in the brain respond to biologically relevant challenges. Here, we combined recent improvements in the temporal resolution of online sampling and analysis for serotonin with a brief high-K(+) stimulus paradigm to study the dynamics of evoked release. We observed stimulated serotonin overflow with high-K(+) pulses as short as 1 min when determined with 2-min dialysate sampling in ventral striatum. Stimulated serotonin levels in female mice during the high estrogen period of the estrous cycle were similar to serotonin levels in male mice. By contrast, stimulated serotonin overflow during the low estrogen period in female mice was increased to levels similar to those in male mice with local serotonin transporter (SERT) inhibition. Stimulated serotonin levels in mice with constitutive loss of SERT were considerably higher yet, pointing to neuroadaptive potentiation of serotonin release. When combined with brief K(+) stimulation, fast microdialysis reveals dynamic changes in extracellular serotonin levels associated with normal hormonal cycles and pharmacologic vs genetic loss of SERT function.

Monitoring Dopamine Responses to Potassium Ion and Nomifensine by in Vivo Microdialysis with Online Liquid Chromatography at One-Minute Resolution

“…Previous studies with K + stimulated 5-HT 25 and DA, 34 using a range of K + concentrations and stimulation times (25 – 120 mM K + for 1–10 min) found that a 50–60 min recovery interval between stimulations is sufficient to avoid the influence of a prior stimulation on the effect of a following stimulation. The range of potassium concentrations and stimulation times encompasses our experimental conditions.…”

Sex differences in abuse-related neurochemical and behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats

“…In contrast to this literature on determinants of DA levels, there is less evidence available with regards to sex differences in the 5HT system. Striatal 5HT levels were higher in the metestrus/diestrus phase of female mice compared to males (Yang et al, 2015), and ventromedial prefrontal cortex 5HT levels were higher in female rats compared to males (Staiti et al, 2011). However, to the best of our knowledge, no studies have examined sex differences in NAc 5HT.…”

Analytical Techniques in Neuroscience: Recent Advances in Imaging, Separation, and Electrochemical Methods

“…92,101 Commercial equipment can be used; for example the 1 minute separations by the Andrews group were performed using commercial equipment. 93 Derivatization of small molecules with benzoyl chloride allows many compounds to be detected simultaneously. EC and MS detection predominate since they are sensitive enough to detect physiological concentrations and require little sample preparation.…”