Effects of D-2 antagonists on frequency-dependent stimulated dopamine overflow in nucleus accumbens and caudate-putamen.

Stimulated dopamine overflow has been measured with in vivo voltammetry in the caudate-putamen and nucleus accumbens. Overflow was induced by electrical stimulation of the medial forebrain bundle with 120 1-ms, 300-microA, biphasic pulses at frequencies between 10 and 60 Hz. Overflow was measured with a Nafion-coated, carbon-fiber electrode used with fast-scan voltammetry (300 V s-1). Quantification and identification of dopamine concentrations down to 100 nM in vivo is possible with this technique. The overflow curves were fit to a kinetic model that describes the measured response as a function of uptake (characterized by a Vmax and Km) and release (characterized by the concentration of dopamine released per stimulus pulse). Overflow curves in both regions could be described with similar kinetic parameters except for the Vmax, which in the nucleus accumbens was only 60% of that measured in the caudate-putamen. Uptake inhibition by nomifensine (20 mg kg-1) caused an apparent 15-fold change in the value of Km in the nucleus accumbens, similar to results previously reported in the caudate-putamen. In contrast, metoclopramide (10 mg kg-1) and sulpiride (100 mg kg-1) altered the apparent amount of dopamine released per stimulus pulse without a change in the uptake kinetics.

Obstetric outcomes at the birth place in Menlo Park: the first seven years.

During its first seven years of operation, the Birth Place, a free-standing birth center in California, registered 898 women, of whom 690 (77%) were admitted in labor and 150 (17%) were referred for hospital birth prior to onset of labor. Using carefully delineated screening criteria, the center had an overall 18% intrapartum transport rate to the hospital, primarily for prolonged or arrested labor, a 3% cesarean section rate, no maternal mortality, and one neonatal death resulting from Cornelia de Lange syndrome, a congenital mental retardation-malformation syndrome of unknown etiology, which in this case was incompatible with life. Deliveries at the Birth Place were associated with low cost, a high level of maternal satisfaction, a low cesarean section rate, low neonatal mortality, and no maternal mortality.

Heterogeneity of stimulated dopamine overflow within rat striatum as observed with in vivo voltammetry.

Overflow of dopamine has been measured in the striatum of anesthetized rats with 60-Hz, 300-microA electrical stimulations of the medial forebrain bundle. Electrodes were placed in the region of the caudate-putamen or the nucleus accumbens. The elliptical electrodes were fabricated from carbon fibers and had a major radius of 35 microns. Overflow was detected with fast-scan voltammetry repeated at 100-ms intervals. In both brain regions the detected substance had the voltammetric properties of dopamine. Measurements were made at different vertical electrode positions, varied by 100-microns intervals. Significant differences in stimulated overflow were observed between each position in both brain regions. The dimensions over which overflow was observed compare to that of previous descriptions of the patch and matrix topology of the striatum. When the electrode was moved in 10-microns intervals the variance was considerably less. The observed rate of overflow during stimulation exactly correlated with the maximal amount of dopamine observed during a stimulation. In addition, the overflow rate and the disappearance rate also correlated. This suggests that in both brain regions uptake and release sites are anatomically close to one another. The major difference between overflow curves measured in the two different regions was the appearance of an apparent mass transfer barrier to the electrode in the caudate-putamen.

Differentiation of dopamine overflow and uptake processes in the extracellular fluid of the rat caudate nucleus with fast-scan in vivo voltammetry.

Stimulated overflow of dopamine (DA) into the extracellular fluid of the rat caudate nucleus was measured with fast-scan cyclic voltammetry. DA concentrations were sampled in less than 10 ms at 100-ms intervals with a Nafion-coated, carbon-fiber microelectrode. Overflow of DA was induced by electrical stimulation of the medial forebrain bundle with 300-microA pulses of various duration and frequency. Stimulated overflow was measured as a function of stimulus duration before and after administration of benztropine, bupropion, and amphetamine. These results were correlated with simulated curves based on a simple uptake/overflow model. The observed overflow was assumed to be a function of [DA]p, the concentration of DA which overflows per stimulus pulse, and the kinetics of cellular uptake of DA. Correlation of experimental with stimulated results was obtained at the 95% confidence limit for the duration studies; however, it was not possible to distinguish between the effects of pharmacological agents on uptake and overflow. In contrast, modulation of stimulus frequency did permit such distinction. Simulations of an increase in [DA]p fit results following dihydroxyphenylalanine methyl ester at 95% confidence limits, whereas an equivalent change in the apparent Km did not fit. An increase in the apparent value of Km correlated with results obtained at different frequencies following nomifensine and bupropion administration at the 95% confidence limit, whereas an equivalent increase in [DA]p did not fit. The effects of GBR 12909 best correlated with an increase in the DA available for overflow.

Real-time characterization of dopamine overflow and uptake in the rat striatum.

The rate of overflow and disappearance of dopamine from the extracellular fluid of the rat striatum has been measured during neuronal stimulation. Overflow of dopamine was induced by electrical stimulation of the medial forebrain bundle with biphasic pulse trains. The instantaneous concentration of dopamine was measured with a Nafion-coated, carbon fiber microelectrode implanted in the brain. The measurement technique, fast-scan cyclic voltammetry, samples the concentration of dopamine in less than 10 ms at 100 ms intervals. Identification of dopamine is made with cyclic voltammetry. Stimulated overflow was measured as a function of electrode position, stimulation duration, stimulation frequency, and after administration of L-DOPA and nomifensine. The observed concentration during a 2-s, 60-Hz stimulation was found to alter with position of the carbon fiber electrode. For stimuli of 3 s or less the amount of overflow was found to be a linear function of stimulus duration at a fixed electrode position. The observed overflow was found to be steady-state at a frequency of 30 Hz, suggesting a balance between uptake and synaptic overflow under these conditions. The experimental data was found to be successfully modelled when the balance of uptake and stimulated overflow was considered. It was assumed that each stimulus pulse releases a constant amount of dopamine (125 nM), and that uptake follows a Michaelis-Menten model for a single uptake site with Km = 200 nM and Vmax = 5 microM/s. The increase in stimulated overflow observed after L-DOPA (250 mg/kg) could be modelled by a 1.6-fold increase in the amount of dopamine release with no alteration of the uptake parameters. The increase in modelled by an increase in Km. In addition, the fit of the modelled data to the experimental data was improved when diffusion from the release and uptake sites was considered.