Zero-net Flux Research Articles

Shedding light on the MRI-driven dynamo in a stratified shearing box

ABSTRACT We study the magneto-rotational instability (MRI) dynamo in a geometrically thin disc (H/R ≪ 1) using stratified zero net (vertical) flux shearing box simulations. We find that mean fields and electromotive forces (EMFs) oscillate with a primary frequency fdyn = 0.017 Ω (approximately nine orbital period), but also have higher harmonics at 3fdyn. Correspondingly, the current helicity has two frequencies 2fdyn and 4fdyn, which appear to be the beat frequencies of mean fields and EMFs, respectively, as expected from the magnetic helicity density evolution equation. Further, we adopt a novel inversion algorithm called the ‘Iterative Removal Of Sources’, to extract the turbulent dynamo coefficients in the mean-field closure using the mean magnetic fields and EMFs obtained from the shearing box simulation. We show that an α-effect (αyy) is predominantly responsible for the creation of the poloidal field from the toroidal field, while shear generates back a toroidal field from the poloidal field, indicating that an α–Ω-type dynamo is operative in MRI-driven accretion discs. We also find that both strong outflow ($\bar{v}_z$) and turbulent pumping (γz) transport mean fields away from the mid-plane. Instead of turbulent diffusivity, they are the principal sink terms in the mean magnetic energy evolution equation. We find encouraging evidence that a generative helicity flux is responsible for the effective α-effect. Finally, we point out potential limitations of horizontal (x − y) averaging in defining the ‘mean’ on the extraction of dynamo coefficients and their physical interpretations.

MRI-driven dynamo at very high magnetic Prandtl numbers

ABSTRACT The dynamo driven by the magnetorotational instability (MRI) is believed to play an important role in the dynamics of accretion discs and may also explain the origin of the extreme magnetic fields present in magnetars. Its saturation level is an important open question known to be particularly sensitive to the diffusive processes through the magnetic Prandtl number Pm (the ratio of viscosity to resistivity). Despite its relevance to proto-neutron stars and neutron star merger remnants, the numerically challenging regime of high Pm is still largely unknown. Using zero-net flux shearing box simulations in the incompressible approximation, we studied MRI-driven dynamos at unprecedentedly high values of Pm reaching 256. The simulations show that the stress and turbulent energies are proportional to Pm up to moderately high values (Pm ∼ 50). At higher Pm, they transition to a new regime consistent with a plateau independent of Pm for $\rm Pm \gtrsim 100$. This trend is independent of the Reynolds number, which may suggest an asymptotic regime where the energy injection and dissipation are independent of the diffusive processes. Interestingly, large values of Pm not only lead to intense small-scale magnetic fields but also to a more efficient dynamo at the largest scales of the box.

Experimental factors affecting in vitro recovery of puerarin in microdialysis

: To analyze experimental factors affecting in vitro recovery of puerarin in microdialysis. : Puerarin concentration in microdialysate samples was determined by high performance liquid chromatography. The methods of direct dialysis, retrodialysis and the zero-net flux were used to calculate in vitro recovery, respectively. The effects of perfusate composition, the analyte concentration, perfusate flow rate, medium temperature and stir rates of the dialysis medium on recovery were investigated. : There were significant differences in the recovery values among direct dialysis, retrodialysis and zero-net flux methods. The recovery for 0.9% NaCl solution, Ringer's solution, PBS and anticoagulant dextrose solution as perfusate fluid were (71.25±2.36)%,(73.48±1.41)%,(68.50±2.43)% and (74.98±1.16)%, respectively. The composition of perfusate fluid had significant influence on the recovery(P<0.01). At the same flow rate, recovery was independent of the analyte concentration. At the same concentration, the recovery was decrease with the increasing flow rate in an exponential relationship. The recovery increased with the raising temperature and stir rate of the dialysis medium, and the recovery remained stable when the stir rate reached above 200 rpm. : A study method for in vitro recovery of puerarin in microdialysis has been established, and the recovery of puerarin is affected by calculating methods, perfusate fluids, flow rate, medium temperature and stir rate, but not affected by analyte concentrations.

Radially dependent large-scale dynamos in global cylindrical shear flows and the local cartesian limit

For cylindrical differentially rotating plasmas, we study large-scale magnetic field generation from finite amplitude non-axisymmetric perturbations by comparing numerical simulations with quasi-linear analytic theory. When initiated with a vertical magnetic field of either zero or finite net flux, our global cylindrical simulations exhibit the magnetorotational instability (MRI) and large scale dynamo growth of radially alternating mean fields, averaged over height and azimuth. This dynamo growth is explained by our analytic calculations of a non-axisymmetric fluctuation-induced EMF that is sustained by azimuthal shear of the fluctuating fields. The standard "Omega effect" (shear of the mean field by differential rotation) is unimportant. For the MRI case, we express the large-scale dynamo field as a function of differential rotation. The resulting radially alternating large-scale fields may have implications for angular momentum transport in disks and corona. To connect with previous work on large scale dynamos with local linear shear and identify the minimum conditions needed for large scale field growth, we also solve our equations in local Cartesian coordinates. We find that large scale dynamo growth in a linear shear flow without rotation can be sustained by shear plus non-axisymmetric fluctuations -- even if not helical, a seemingly previously unidentified distinction. The linear shear flow dynamo emerges as a more restricted version of our more general new global cylindrical calculations.

Turbulent Convection Insights from Small-Scale Thermal Forcing with Zero Net Heat Flux at a Horizontal Boundary.

A large-scale circulation, a turbulent boundary layer, and a turbulent plume are noted features of convection at large Rayleigh numbers under differential heating on a single horizontal boundary. These might be attributed to the forcing, which in all studies has been limited to a unidirectional gradient over the domain scale. We instead apply forcing on a length scale smaller than the domain, and with variation in both horizontal directions. Direct numerical simulations show turbulence throughout the domain, a regime transition to a dominant domain-scale circulation, and a region of logarithmic velocity in the boundary layer, despite zero net heat flux. The results show significant similarities to Rayleigh-Bénard convection, demonstrate the significance of plume merging, support the hypothesis that the key driver of convection is the production of available potential energy without necessarily supplying total potential energy, and imply that contributions to domain-scale circulation in the oceans need not be solely from the large-scale gradients of forcing.

Potentiated Striatal Dopamine Release Leads to Hyperdopaminergia in Female Brain-Derived Neurotrophic Factor Heterozygous Mice

The goal of this study was to determine whether a reduction in brain-derived neurotrophic factor (BDNF) levels in female mice leads to dopaminergic system dysregulation. Through a series of in vivo brain microdialysis and slice voltammetry experiments, we discerned that female BDNF heterozygous (BDNF(+/-)) mice are hyperdopaminergic, similar to their male BDNF(+/-) counterparts. Zero-net flux microdialysis results showed that female BDNF(+/-) mice had increased striatal extracellular dopamine levels, while stimulated regional release by high potassium concentrations potentiated dopamine release through vesicular-mediated depolarization. Using the complementary technique of fast scan cyclic voltammetry, electrical stimulation evoked greater dopamine release in the female BDNF(+/-) mice, whereas dopamine uptake remained unchanged relative to that of female wildtype mice. Following psychostimulant methamphetamine administration, female BDNF(+/-) mice showed potentiated dopamine release compared to their wildtype counterparts. Taken together, these dopamine release impairments in female mice appear to result in a hyperdopaminergic phenotype without concomitant alterations in dopamine uptake.

MHD simulations of the magnetorotational instability in a shearing box with zero net flux: the case Pm = 4

<i>Aims. <i/>This letter investigates the transport properties of MHD turbulence induced by the magnetorotational instability at large Reynolds numbers <i>Re<i/> when the magnetic Prandtl number <i>Pm<i/> is larger than unity.<i>Methods. <i/>Three MHD simulations of the magnetorotational instability (MRI) in the unstratified shearing box with zero net flux are presented. These simulations are performed with the code Zeus and consider the evolution of the rate of angular momentum transport as <i>Re<i/> is gradually increased from 3125 to 12 500 while simultaneously keeping <i>Pm<i/> = 4. To ensure that the small scale features of the flow are well resolved, the resolution varies from 128 cells per disk scaleheight to 512 cells per scaleheight. The latter constitutes the highest resolution of an MRI turbulence simulation to date.<i>Results. <i/>The rate of angular momentum transport, measured using the <i>α<i/> parameter, depends only very weakly on the Reynolds number: <i>α<i/> is found to be about 7 × 10<sup>-3<sup/> with variations around this mean value bounded by 15% in all simulations. There is no systematic evolution with <i>Re<i/>. For the best resolved model, the kinetic energy power spectrum tentatively displays a power-law range with an exponent -3/2, while the magnetic energy is found to shift to smaller and smaller scales as the magnetic Reynolds number increases. A couple of different diagnostics both suggest a well-defined injection length of a fraction of a scaleheight.<i>Conclusions. <i/>The results presented in this letter are consistent with the MRI being able to transport angular momentum efficiently at large Reynolds numbers when <i>Pm<i/> = 4 in unstratified zero net flux shearing boxes.

Zero net flux estimates of septal extracellular glucose levels and the effects of glucose on septal extracellular GABA levels

Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated. For instance, hippocampal glucose infusions reverse the memory-impairing effects of co-infusions of the GABA agonist muscimol, whereas septal glucose infusions exacerbate memory deficits produced by muscimol. One potential explanation for these deleterious effects of glucose in the septum is that there are higher levels of endogenous extracellular fluid glucose concentrations in the septum than in the hippocampus. Another hypothesis is that septal glucose infusions impair memory by increasing septal GABA synthesis or release, which is possible because elevating glucose increases GABA levels in other brain regions. To test these hypotheses, Experiment 1 quantified extracellular fluid glucose levels in the septum and hippocampus using zero net flux in vivo microdialysis procedures in conscious, freely moving rats. Experiment 2 determined whether septal infusions of glucose would increase GABA concentrations in dialysates obtained from the septum. The results of Experiment 1 indicated that extracellular fluid glucose levels in the hippocampus and septum are comparable. The results of Experiment 2 showed that co-infusions of glucose with muscimol, at doses that did not affect memory on their own, decreased percent alternation memory scores. However, none of the infusions significantly affected GABA levels. Collectively, these findings suggest that the memory-impairing effects of septal infusions of glucose are not likely due to regional differences in basal extracellular fluid glucose concentrations and are not mediated via an increase in septal GABA release.

On self-sustained dynamo cycles in accretion discs

Context. MHD turbulence is known to exist in shearing boxes with either zero or nonzero net magnetic flux. However, the way turbulence survives in the zero-net-flux case is not explained by linear theory and appears as a purely numerical result that is not well understood. This type of turbulence is also related to the possibility of having a dynamo action in accretion discs, which may help to generate the large-scale magnetic field required by ejection processes. Aims. We look for a nonlinear mechanism able to explain the persistence of MHD turbulence in shearing boxes with zero net magnetic flux, and potentially leading to large-scale dynamo action. Methods. Spectral nonlinear simulations of the magnetorotational instability are shown to exhibit a large-scale axisymmetric magnetic field, maintained for a few orbits. The generation process of this field is investigated using the results of the simulations and an inhomogeneous linear approach. We show that quasilinear nonaxisymmetric waves may provide a positive back-reaction on the largescale field when a weak inhomogeneous azimuthal field is present, explaining the behaviour of the simulations. We finally reproduce the dynamo cycles using a simple closure model summarising our linear results. Results. The mechanism by which turbulence is sustained in zero-net-flux shearing boxes is shown to be related to the existence of a large-scale azimuthal field, surviving for several orbits. In particular, it is shown that MHD turbulence in shearing boxes can be seen as a dynamo process coupled to a magnetorotational-type instability.

Strain differences in basal and post‐citalopram extracellular 5‐HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase‐2 activity

We used the microdialysis technique to compare basal extracellular serotonin (5-HT) and the response to citalopram in different strains of mice with functionally different allelic forms of tryptophan hydroxylase-2 (TPH-2), the rate-limiting enzyme in brain 5-HT synthesis. DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele of TPH-2 had less dialysate 5-HT in the medial prefrontal cortex and dorsal hippocampus (DH) (20-40% reduction) than C57BL/6J and C57BL/6N mice carrying the 1473C allele. Extracellular 5-HT estimated by the zero-net flux method confirmed the result of conventional microdialysis. Citalopram, 1.25, 5 and 20 mg/kg, dose-dependently raised extracellular 5-HT in the medial prefrontal cortex of C57BL/6J mice, with maximum effect at 5 mg/kg, but had significantly less effect in DBA/2J and BALB/c mice and in the DH of DBA/2J mice. A tryptophan (TRP) load enhanced basal extracellular 5-HT in the medial prefrontal cortex of DBA/2J mice but did not affect citalopram's ability to raise cortical and hippocampal extracellular 5-HT. The impairment of 5-HT synthesis quite likely accounts for the reduction of basal 5-HT and the citalopram-induced rise in mice carrying the mutated enzyme. These findings might explain why DBA/2 and BALB/c mice do not respond to citalopram in the forced swimming test. Although TRP could be a useful strategy to improve the antidepressant effect of citalopram (Cervo et al. 2005), particularly in subjects with low 5-HT synthesis, the contribution of serotonergic and non-serotonergic mechanisms to TRP's effect remains to be elucidated.

Assessment of in vitro and in vivo recovery of sinomenine using microdialysis

For microdialysis studies in the skin, laboratory-made linear probes are often used. The application of the microdialysis technique to the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of the linear probes' performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investigation of the pharmacokinetics and pharmacodynamics of sinomenine. Using different lengths of the dialysis membrance and different perfusion flow rates, a flow rate of 2 microL/min with 20-min sampling intervals was selected for the subsequent studies, based on the analysis of sinomenine from the microdialysis probe. In vitro recovery of sinomenine from the microdialysis probe was independent of concentration, stable over an 8-h period. Comparable in vitro recoveries were obtained by different established approaches including recovery estimation by gain, loss and the zero-net flux (ZNF) method. Recovery by loss was used to study the in vivo recovery of sinomenine from rat subcutaneous tissue. The performance of the microdialysis system was stable over an 8-h study, resulting in a mean in vitro recovery of 51.91+/-1.29%. Recovery obtained using the ZNF plot was 52.43%. In vivo recovery of sinomenine was 34.46+/-0.76% and was stable over the 7-h study period. The in vitro and in vivo performance of the microdialysis technique was established for the study of sinomenine. It would prove to be a useful and reliable tool to study the pharmacokinetics and pharmacodynamics of sinomenine. The data obtained in our study highlight the importance of a systematic examination of microdialysis linear probe validation.

Effects of tissue trauma on the characteristics of microdialysis zero-net-flux method sampling neurotransmitters

Microdialysis has been used for studying neurochemistry in brain regions that respond to afferent inputs or administered drugs. As the knowledge derived from and concerning microdialysis grows, so do the concerns over its invasiveness and, hence, the credibility of resulting data. Recent experimental and theoretical studies impugned the validity of the microdialysis zero-net-flux (ZNF) method in measuring brain extracellular neurotransmitters, suggesting that the tissue trauma resulting from probe implantation seriously compromises its worth. This paper developed a theoretical model to study the influences of two categories of tissue trauma on microdialysis ZNF operation: (1) morphological alterations in tissue extracellular structure and (2) physiological impairment of neurotransmitter release and uptake processes. Model results show that alterations of tissue extracellular structure negligibly affect the accuracy of the ZNF method in determining the basal level of extracellular neurotransmitter but do affect the fundamental characteristics of microdialysis: the extraction efficiency and relative recovery. An inhibited or damaged neurotransmitter uptake process always decreases the efficiency of microdialysis extraction, but rise of the relative recovery of neurotransmitters with the same uptake inhibition/damage occurs only when there is far more damage to the neurotransmitter release than to the uptake process in the tissue. A criterion for this rising trend of microdialysis relative recovery is discussed in terms of trauma parameters and neurotransmitter uptake inhibition.

Preferentially impaired neurotransmitter release sites not their discreteness compromise the validity of microdialysis zero‐net‐flux method

Intracerebral microdialysis is a popular technique for studying neurochemistry and neural circuits in various brain regions. Recent studies called into question the validity of the microdialysis zero-net-flux (ZNF) method by suggesting that this method significantly underestimates the basal level of extracellular dopamine as a result of the discreteness of dopamine release sites as well as the preferential damage to dopamine release over uptake. To identify which factor is most important in undermining the microdialysis ZNF measurements and the extent of underestimation, two mathematical models were developed to explore the influences of the discrete nature and the probe-induced impairment in the neurotransmitter release. The two models differ in their characterizations of the transmitter release as spatially discrete and homogeneous, respectively. Simulations using physiologically reasonable parameters for striatal dopamine systems indicate that the preferential release site damage surrounding the implanted probe is the most important determinant to the underestimation of the microdialysis ZNF concentration. Under normal physiological conditions, the discreteness of neurotransmitter release sites is of minor importance, except when neuronal degeneration occurs. It is concluded that homogeneous models can adequately describe microdialysis operating processes as long as the corresponding tissue damage parameters in such models are appropriately incorporated.

Evidence on extracellular dopamine level in rat striatum: implications for the validity of quantitative microdialysis

Microdialysis zero-net-flux (ZNF) method is commonly used to monitor drug-induced changes in neurotransmitter baseline and release/uptake processes. Recent studies in this field suggest that microdialysis ZNF method seriously underestimates the resting concentration of extracellular dopamine in the rat neostriatum because probe implantation preferentially damages nearby dopamine release sites and that dopamine uptake inhibition increases the relative recovery of dopamine by microdialysis. This study assessed the validity of these claims by examining current data on extracellular dopamine levels at rest and after drug application obtained by voltammetry, a technique thought to induce less tissue disruption than microdialysis. To obtain the extracellular baseline value for dopamine from the evoked overflow data, we modified the existing dopamine kinetic model to suit both the resting and stimulated circumstances. It was found that dopamine uptake inhibition did in fact decrease the microdialysis relative recovery of dopamine, implying that the average basal extracellular dopamine level is within the range of 7-20 nm in rat striatum. This study concludes that the microdialysis ZNF method indeed underestimates the extracellular dopamine concentration, although not by as much as had been thought. Chronic microdialysis damages both neurotransmitter release and uptake, but it does so in a somewhat relative and proportional way for both processes. Thus the validity of the microdialysis ZNF method is not seriously undermined.

Excised porcine skin experimental systems to validate quantitative microdialysis methods for determination of drugs in skin after topical application

Microdialysis is useful as a method to evaluate the disposition of drugs in the skin to design improved transdermal delivery systems (TDDSs). In this study, quantitative microdialysis methods were validated in excised porcine skin experimental systems in vitro. Flurbiprofen (FP), used as a model drug, showed high affinity for the skin tissues in equilibrium states between the medium and skin. The membrane clearances of FP for permeation through the membrane of a dialysis fiber placed in the skin (CL m in S) were lower than that in the medium. The adsorption of components in the skin to the membrane surface of the dialysis fiber and accumulation of FP near the dialysis fiber are the most likely reasons for this. When CL m in S was used to predict the extracellular FP concentration in skin ( C T), the value obtained was lower than that expected from the FP concentration in the medium on the dermis side, which should be equal to C T at equilibrium. In the zero net flux (ZNF) method, in which the concentration difference of perfusate (Δ C) between the inflow and outflow were used to obtain C T, the predicted C T was similar to the expected value. In an in vitro skin permeation experiment, the ZNF method was used for the prediction of C T near the dialysis fiber. The predicted C T was over 10 times higher than the FP concentration in the medium on the dermis side, suggesting a concentration gradient in the dermis. Although the ZNF method is good for predicting the C T in skin, the mass balance has to be considered for the quantitative evaluation of the skin permeation of drugs. In this study, the effect of the mass transfer of FP from the perfusate to the skin on the cumulative amount of FP passing through the skin was relatively low because of the use of suitable solutions as perfusate. The perfusion conditions and schedules should be designed carefully for quantitative evaluations using the ZNF method. These results provide useful information for the in vivo application of quantitative microdialysis to evaluate TDDS.

Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression

Serotonin (5-HT) plays an integral regulatory role in mood, anxiety, cognition, appetite and aggressive behavior. Many therapeutic and illicit drugs that modulate these functions act at the serotonin transporter (SERT), thus a mouse model with reduced transporter expression was created to further investigate the effects of differential serotonin reuptake. In the present study, in vivo microdialysis was used to determine homeostatic alterations in extracellular 5-HT levels in unanesthetized SERT knockout mice. SERT −/− mice had significantly higher levels of basal dialysate 5-HT than SERT +/+ mice in striatum and frontal cortex. In addition, although gene-specific increases in 5-HT were evident, neuroadaptive alterations in dialysate dopamine levels were not detected in striatum. Zero net flux microdialysis was utilized to further investigate alterations in extracellular 5-HT. Using this method, a gene dose-dependent increase in extraneuronal 5-HT was observed in striatum (2.8 ± 1, 9.4 ± 1 and 18 ± 3 nM) and frontal cortex (1.4 ± 0.4, 3.5 ± 0.9 and 14 ± 1 nM) in SERT +/+, SERT +/− and SERT −/− mice, respectively. Potassium stimulation revealed greater depolarization-induced increases in striatal 5-HT but not dopamine in SERT −/− mice. Furthermore, dialysate 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in striatum in a gene dose-dependent manner, while DOPAC was unchanged in SERT knockout mice. Finally, determination of monoamine oxidase (MAO) activity revealed no significant differences in K M or V max of type-A or type-B isozymes indicating that alterations in SERT expression do not cause adaptive changes in the activities of these key catabolic enzymes. Overall, these results demonstrate that constitutive reductions in SERT are associated with increases in 5-HT in the extracellular signaling space in the absence of changes in dopamine neurochemistry. Furthermore, use of zero net flux microdialysis appears warranted in investigations of serotonergic synaptic function where modest changes in extracellular 5-HT are thought to occur in response to altered uptake.

Insensitivity of the microdialysis zero-net-flux method to nonlinear uptake and release processes

In the microdialysis zero-net-flux (ZNF) method the extraction efficiency is conventionally obtained by linear regression. The linear analysis may become invalid for certain analytes that have nonlinear uptake/release processes in the tissue. To examine this hypothesis, a nonlinear model was used to numerically investigate the nonlinearity of the ZNF plot caused by nonlinear uptake and release processes. Three findings from this analysis are: (i) the ZNF method is markedly insensitive to the nonlinear active processes; (ii) a slow infusion rate or a long probe membrane can suppress the nonlinearity; (iii) the release under autoreceptor control does not affect the slope and linearity of the concentration difference plot. It is concluded that in the nM infusion range, the ZNF method is unable to distinguish whether or not the tissue clearance process is nonlinear. During electrical stimulation, neurotransmitter overflow may cause the microdialysis ZNF method to exhibit nonlinearity.

The Effect of the Hall Term on the Nonlinear Evolution of the Magnetorotational Instability. I. Local Axisymmetric Simulations

The effect of the Hall term on the evolution of the magnetorotational instability (MRI) in weakly ionized accretion disks is investigated using local axisymmetric simulations. First, we show that the Hall term has important effects on the MRI when the temperature and density in the disk is below a few thousand K and between 1013 and 1018 cm-3, respectively. Such conditions can occur in the quiescent phase of dwarf nova disks, or in the inner part (inside 10-100 AU) of protoplanetary disks. When the Hall term is important, the properties of the MRI are dependent on the direction of the magnetic field with respect to the angular velocity vector Ω. If the disk is threaded by a uniform vertical field oriented in the same sense as Ω, the axisymmetric evolution of the MRI is an exponentially growing two-channel flow without saturation. When the field is oppositely directed to Ω, however, small scale fluctuations prevent the nonlinear growth of the channel flow and the MRI evolves into MHD turbulence. These results are anticipated from the characteristics of the linear dispersion relation. In axisymmetry on a field with zero-net flux, the evolution of the MRI is independent of the size of the Hall term relative to the inductive term. The evolution in this case is determined mostly by the effect of ohmic dissipation.

Assessment of in vitro and in vivo recovery of gallamine using microdialysis

The application of microdialysis technique for the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of probe performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investigation of the pharmacokinetics and pharmacodynamics of the neuromuscular blocker, gallamine. In vitro recovery of gallamine from the microdialysis probe when different perfusion flow rates were employed was evaluated leading to selection of a flow rate of 2 μl/min with 15-min sampling intervals for the subsequent studies. In vitro recovery of gallamine from the microdialysis probe was independent of concentration, stable over an 8-h period and reproducible. Comparable in vitro recoveries were obtained by different established approaches including recovery estimation by gain, loss and the zero-net flux (ZNF) method. Recovery by loss was used to study the in vivo recovery of gallamine from rat muscle tissue. The in vivo recovery was stable over a 5.5-h sampling period. In vitro performance of the probe subsequent to the in vivo study remained stable supporting reusage of the probe. These data highlight the importance of a systematic examination of microdialysis probe validation.

Effects of different perfusion medium on the extracellular basal concentration of dopamine in striatum and medial prefrontal cortex: a zero-net flux microdialysis study

The zero-net flux microdialysis method was used to determine (1) the basal concentration of dopamine (DA) in the extracellular space, and (2) the in vivo recovery of DA in the striatum and the medial prefrontal cortex by using three different kinds of perfusion medium. They were, (a) commercial Ringer's solution, (b) low Ca2+ Ringer's solution, and (c) artificial cerebrospinal fluid (aCSF). Our results not only support previous findings that the high Ca2+ concentration in the perfusion medium could increase the baseline concentration of DA in the dialysate, which was collected from extracellular space through dialysis probe; but also provides evidence that this baseline increase was primarily due to an increase of basal DA concentration, and not from the increase of the in vivo recovery. Additionally, there was no significant difference in the basal DA concentration by using either commercial Ringer's solution or aCSF. This indicates that both commercial Ringer's solution and aCSF are suitable as good perfusion medium to determine the basal DA in the rat's brain.