Microdialysis concentric

Figure 4,7 The effect of perfusion of the microdialysis probe with a medium containing a depolarising (80 mM) concentration of K" ", or Ca +-free medium, for the periods indicated by the bars. The graph shows efflux of noradrenaline in the frontal cortex of anaesthetised rats. Increasing the concentration of K" " in the medium infused via the probe increases noradrenaline efflux whereas removing Ca reduces it...

Figure 4.8 Noradrenaline concentration in dialysis samples from probes implanted in the rat frontal cortex. Spontaneous efflux of noradrenaline is stable throughout a 4h sampling period ( extended basals ) but is increased markedly when either the noradrenaline reuptake inhibitor, desipramine (5 pM), or the a2-adrenoceptor antagonist, atipamezole (0.5 pM), is infused into the extracellular fluid via the microdialysis probe ( retrodialysis )...

The comparatively straightforward link between 5-HT and its primary metabolite, 5-HIAA, encouraged many researchers to use changes in the ratio of tissue concentrations of 5-HIAA and 5-HT as an index of the rate of release of 5-HT ex vivo. However, it has been clear for some time that the majority of 5-HT is metabolised in the cytoplasm by MAO before it is released from 5-HT nerve terminals. Consequently, the reliability of the 5-HIAA 5-HT ratio as an index of transmitter release is rather dubious, although it could be used as an acceptable measure of MAO activity. In any case, the development of in vivo microdialysis means that changes in the concentration of extracellular 5-HT can now be monitored directly which, under drug-free conditions, provides a far more reliable indication of any changes in the rate of release of 5-HT. 

As described above, because MAO is bound to mitochondrial outer membranes, MAOIs first increase the concentration of monoamines in the neuronal cytosol, followed by a secondary increase in the vesicle-bound transmitter. The enlarged vesicular pool will increase exocytotic release of transmitter, while an increase in cytoplasmic monoamines will both reduce carrier-mediated removal of transmitter from the synapse (because the favourable concentration gradient is reduced) and could even lead to net export of transmitter by the membrane transporter. That MAOIs increase the concentration of extracellular monoamines has been confirmed using intracranial microdialysis (Ferrer and Artigas 1994). 

A link between 5-HT release and increased waking is supported by evidence from in vivo microdialysis of cats and rats. This has confirmed that the extracellular concentration of 5-HT in all brain regions studied to date is lower during both SWS and REM sleep than in the awake state (see Portas, Bjorvatn and Ursin 2000). Interestingly, if behaviour is maintained at a constant level, the activity of 5-HT neurons does not show circadian variation although 5-HT turnover in the brain areas to which they project... 

Figure 1.6 (A) Changes in c-Fos IR in hypocretin/orexin(HCRT+)- containing neurons in response to BIC treatment as a function of distance from the microdialysis probe. The percentage of double-labeled cells was greatest closer to the probe (grids 1 and 2, compared with 3 and 4) and was greater with higher concentrations or exposure times. Contralateral cells were not affected. (B) Much lower percentages of melanin-concentrating hormone (MCH+) exhibited c-Fos IR activation in response to BIC. From Alam et al. (2005).

Porkka-Heiskanen, T., Strecker, R. E. McCarley, R. W. (2000). Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep an in vivo microdialysis study. Neuroscience 99, 507-17. 

Figure 12.1 Extracellular adenosine concentrations in different brain areas, measured with in vivo microdialysis from cats during sleep deprivation (6 h gentle handling) and recovery sleep. Concentrations are given as a percentage of pre-deprivation values. BF, basal forebrain CX, cingulate cortex TH, VA/VL nucleus of thalamus POA, preoptic hypothalamic area DRN, dorsal raphe nucleus PPT, pedunculopontine nucleus. In BF and CX adenosine rises during sleep deprivation, but starts to decline during deprivation in CX, whereas the decline occurs during recovery in the BF. In other areas there is no accumulation during sleep deprivation. Modified from Porkka-Heiskanen et al. (2000).

FIGURE 1.10 Laser-doppler flowmetry (a) and NO measurement (b) from one subject. Upon heating the subject to 39°C, at 10 min, NO production and skin blood flow increased, which instantly returned to normal upon cooling the subject at 45 min. After heat stress and cooling, ACh was administered by intra-dermal microdialysis to confirm the ability of the microelectrode to measure NO concentrations. (Reprinted with permission from the American Physiological Society [125].)... 

BMS-505130 (7) is a potent and selective serotonin transporter inhibitor (SERT K< = 0.18 nM, NET K< — 4.6 gM, DAT K< — 2.1 (tM). In brain microdialysis studies, 7 demonstrated a dose-dependent increase in cortical serotonin levels. Compound 7 was also active in the mouse tail suspension model [15]. Following oral administration, peak plasma concentration of 7 was reached at 1.6 h and then declined to a concentration less than 10% of Cmax within 6 h. The short half-life of 7 might be advantageous for the treatment of PE where an acute effect to delay ejaculation followed by a relatively rapid fall in SSRI plasma concentration might be desirable. 

A number of recent publications indicate that the antibacterial field has adopted the concept of comparing free drug concentration at the site of action to in vitro drug potency reported as MIC [24-26]. A study of the antibacterial ertapenem in healthy volunteers was carried out to provide support for its use in skin and skin-structure infections [27]. Using microdialysis techniques, unbound drug concentrations in muscle and subcutaneous tissues were sampled at... 

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