Microdialysis levels

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... 

Kala SV, Jadhav AL. 1995b. Low level lead exposure decreases in vivo release of dopamine in the rat nucleus accumbens A microdialysis study. J Neurochem 65 1631-1635. 

Strecker, R. E., Nalwalk, J., Dauphin, L. J. et al. (2002). Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness an in vivo microdialysis study. Neuroscience 113, 663-70. 

Iwakiri, H., Matsuyama, K. Mori, S. (1993). Extracellular levels of serotonin in the medial pontine reticular formation in relation to sleep-wake cycle in cats a microdialysis study. Neurosci. Res. 18, 157-70. 

Pistis, M., Ferraro, L., Flore, G., Tanganelli, S., Gessa, G.L., and Devoto, P., Delta(9)-tetrahydrocan-nabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the prefrontal cortex an in vivo microdialysis study, Brain Res., 948, 155, 2002. 

Bradberry, C.W., Nobiletti, J.B., Elsworth, J.D., Murphy, B., Jatlow, R, and Roth, R.H., Cocaine and cocaethylene microdialysis comparison of brain drug levels and effects on dopamine and serotonin, J. Neurochem., 60, 1429, 1993. 

Figure 7.4 Dose-response effects of MDMA on extracellular levels of endogenous 5-HT (left panel) and DA (right panel) in rat nucleus accumbens. Male rats undergoing in vivo microdialysis received i.v. injections of 1 and 3 mg/kg MDMA at 0 and 60 min, respectively. Dialysate levels of 5-HT and DA were assayed by HPLC-ECD. Data are mean SEM, expressed as pg/5 pi sample, for N = 6 rats/group. Baseline levels of 5-HT and DA were 0.22 0.03 and 1.44 0.24 pg/5 pi, respectively. Significant with respect to pre-injection control (P < 0.05 Duncan s). See Baumann et al.39 for methods.

In vivo microdialysis has been used to evaluate the persistent neurochemical consequences of MDMA exposure in rats.88114-116 Series et al.114 carried out microdialysis in rat frontal cortex 2 weeks after a 4-day regimen of 20 mg/kg s.c. MDMA. Prior MDMA exposure did not affect baseline extracellular levels of 5-HT, but decreased levels of the 5-HT metabolite, 5-hydroxyin-doleacetic acid (5-HIAA), to 30% of control. Moreover, the ability of (+)-fenfluramine to evoke 5-HT release was markedly blunted in MDMA-pretreated rats. In an analogous investigation, Shankaran and Gudelsky115 assessed neurochemical effects of acute MDMA challenge in rats that had previously received 4 doses of 10 mg/kg i.p. MDMA. A week after MDMA pretreatment, baseline levels of dialysate 5-HT and DA in striatum were not altered even though tissue levels of 5-HT were depleted by 50%. The ability of MDMA to evoke 5-HT release was severely impaired in MDMA-pretreated rats while the concurrent DA response was normal. In this same study, effects... 

Baumann, M.H. and Rutter, J.J., Application of in vivo microdialysis methods to the study of psychomotor stimulant drugs, in Methods in Drug Abuse Research, Cellular and Circuit Level Analysis, Warerhouse, B.D., Ed., CRC Press, Boca Raton, FL, 2003, 51-86. 

Hall, F.S., Devries, A.C., Fong, G.W., Huang, S., and Pert, A., Effects of 5,7-dihydroxytryptamine depletion of tissue serotonin levels on extracellular serotonin in the striatum assessed with in vivo microdialysis relationship to behavior, Synapse 33(1), 16-25, 1999. 

SSR-504734 is a potent, selective, and reversible inhibitor (IC50 = 18 nM) that is competitive with glycine [47,51]. The inhibitor rapidly and reversibly blocked the uptake of [14C]glycine in mouse cortical homogenates, which was sustained for up to 7 h. Complete cessation of blockade and return to glycine basal levels occurred prior to 24 h, which is in stark contrast to NFPS (>24 h). SSR-504734 potentiated a nearly twofold increase of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal slices and produced an increase in contralateral rotations in mice when microinjected into the striatum. Microdialysis experiments indicated that the inhibitor induced a rapid and sustained increase in extracellular glycine levels in the PFC of freely moving rats [51]. The compound also demonstrated efficacy in a variety of psychosis models [51-53]. SSR-504734 was reportedly in clinical trials for schizophrenia but discontinued after Phase I (data not disclosed) [54]. 

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 microdialysis study was carried out to examine transport of oxycodone into the brain of rats [67], Oxycodone was administered by i.v. infusion, and unbound drug concentrations were monitored in both vena jugularis and striatum. Steady-state equilibrium was reached rapidly and drug levels in the two compartments declined in parallel at the end of the infusion. An unbound brain to unbound plasma ratio of 3.0 was measured which is 3- to 10-fold higher than for other opioids, and explains the similar in vivo potency of oxycodone in spite of lower receptor affinity. The authors interpret these data as de facto evidence of the existence of an as-yet unidentified transporter that carries oxycodone across the blood-brain barrier. 

Originating from the neurosciences, the microdialysis technique has been used since several years to monitor drug absorption and disposition or the levels of endogenous substances in the extracellular space of different organs and fluids, such as bone, lung, liver, brain, and blood. The method has evolved from its use in different animal species to the human microdialysis during the late 80s [35],... 

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