Dopaminergic transmission in STOP null mice.

Neuroleptics are thought to exert their anti-psychotic effects by counteracting a hyper-dopaminergic transmission. Here, we have examined the dopaminergic status of STOP (stable tubule only polypeptide) null mice, which lack a microtubule-stabilizing protein and which display neuroleptic-sensitive behavioural disorders. Dopamine transmission was investigated using both behavioural analysis and measurements of dopamine efflux in different conditions. Compared to wild-type mice in basal conditions or following mild stress, STOP null mice showed a hyper-locomotor activity, which was erased by neuroleptic treatment, and an increased locomotor reactivity to amphetamine. Such a behavioural profile is indicative of an increased dopaminergic transmission. In STOP null mice, the basal dopamine concentrations, measured by quantitative microdialysis, were normal in both the nucleus accumbens and the striatum. When measured by electrochemical techniques, the dopamine efflux evoked by electrical stimulations mimicking physiological stimuli was dramatically increased in the nucleus accumbens of STOP null mice, apparently due to an increased dopamine release, whereas dopaminergic uptake and auto-inhibition mechanisms were normal. In contrast, dopamine effluxes were slightly diminished in the striatum. Together with previous results, the present study indicates the association in STOP null mice of hippocampal hypo-glutamatergy and of limbic hyper-dopaminergy. Such neurotransmission defects are thought to be central to mental diseases such as schizophrenia.

Capillary electrophoresis combined with microdialysis in the human spinal cord: a new tool for monitoring rapid peroperative changes in amino acid neurotransmitters within the dorsal horn.

A method originally developed for the separation of the three neurotransmitters gamma-aminobutyric acid (GABA), glutamate (Glu) and L-aspartate (L-Asp) in microdialysis samples from rat brain (Sauvinet et al., Electrophoresis 2003, 24, 3187-3196) was applied to human spinal dialysates obtained during peroperative microdialysis from patients undergoing surgery against chronic pain. Molecules were tagged on their primary amine function with the fluorogene agent, naphthalene-2,3-dicarboxaldehyde (NDA), and, after separation by capillary electrophoresis (CE, 75 mmol/L borate buffer, pH 9.2, containing 70 mmol/L sodium dodecyl sulfate and 10 mmol/L hydroxypropyl-beta-cyclodextrin, + 25 kV voltage), were detected by laser-induced fluorescence detection (LIFD) using a 442 nm helium-cadmium laser. The complete method, including microdialysis sampling and analysis by CE-LIFD, has been validated for the analysis of human spinal microdialysates. The analytical detection limits were 1, 3.7 and 17 nmol/L for GABA, Glu and L-Asp respectively. This method allows an accurate measurement of the three amino acid neurotransmitters during an in vivo monitoring performed as rapidly as every minute in the human spinal dorsal horn. In addition, the effect of a brief peroperative electrical stimulation of the dorsal rootlets was investigated. The results obtained illustrate the advantages of combining microdialysis with CE-LIFD for studying neurotransmitters with such a high sampling rate.

Microdialysis monitoring of catecholamines and excitatory amino acids in the rat and mouse brain: recent developments based on capillary electrophoresis with laser-induced fluorescence detection--a mini-review.

1. Although microdialysis is a widely used approach for in vivo monitoring extracellular neurotransmitter concentrations, it has been previously limited in many cases by its poor temporal resolution. It is clear that when 10-30-min sampling is performed, short-lasting changes in extracellular neurotransmitter concentrations can be overlooked. Such a low sampling rate is necessary when combining microdialysis with the conventional analytical methods like high performance liquid chromatography. 2. Since capillary electrophoresis coupled to laser-induced fluorescence detection (CE-LIFD) allows the detection of attomoles of neurotransmitters, the temporal resolution of microdialysis may be significantly improved: high sampling rates, in the range of 5 s to 1 min, have been already reported by our group and others using CE-LIFD for simultaneously analyzing catecholamines and amino acids in microdialysates. 3. The power of combining microdialyis and CE-LIFD is shown, using examples of physiological and pharmacological studies dealing with the dynamics of in vivo efflux processes and/or interactions between neurotransmitters.