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J B Justice

Publications and source records attributed to J B Justice.

At least 91 records · Page 5Linked to original sources
PubMed1988

Extracellular cocaine and dopamine concentrations are linearly related in rat striatum.

Microdialysis and gas chromatography/mass spectrometry were used to determine temporal cocaine concentration profiles in the rat striatum following intraperitoneal (i.p.) cocaine injection. For a 30 mg/kg i.p. dose, cocaine reached a maximum in vivo concentration of 10.1 microM within 30 min, and then rapidly declined. A non-linear fit of a kinetic model to the experimental cocaine data gave a first-order rate constant for the appearance of cocaine in the extracellular fluid of the striatum after a 30 mg/kg dose of cocaine of 0.0304/min and a first-order rate constant of 0.0386/min for the disappearance of cocaine from the extracellular fluid. When combined with previous dopamine results for a 30 mg/kg i.p. cocaine dose, cocaine concentrations were found to be highly correlated (r = 0.963) with dopamine concentrations for the same point in time. The slope was 36.8 nM dopamine/microM cocaine and the y-intercept was 29.9 nM dopamine. Maximum dopamine and maximum cocaine concentrations were also found to be linearly related to i.p. dose of cocaine for doses of 3, 10, and 30 mg/kg.

Animals↗
PubMed1988

Effects of cocaine on release and uptake of dopamine in vivo: differentiation by mathematical modeling.

Although considerable effort has been invested trying to distinguish between the effects of cocaine on dopamine (DA) uptake and release in both in vitro and in vivo experiments, disagreement over the specific actions of cocaine remains. The results obtained by combining experimental extracellular DA data with a mathematical model of the dopaminergic neuron allow examination of the cocaine uptake inhibition/release question. The extracellular DA concentration profile observed following a 30 mg/kg IP cocaine injection can be modeled if both pre- and postsynaptic uptake are competitively inhibited by cocaine with or without an enhanced DA release effect. However, if cocaine elicits enhanced DA release, modeling predicts a 40% increase over basal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and a 30% increase in homovanillic acid (HVA) at 60 minutes following a 30 mg/kg IP cocaine injection. Reported DOPAC and HVA data for similar cocaine doses indicate little change in either DOPAC or HVA. These data agree best with modeled metabolite predictions for little or no cocaine-enhanced DA release.

Cocaine↗
PubMed1988

Modeling the dopaminergic nerve terminal.

A method is described for developing and evaluating models of neurochemical processes. Computer simulation and simplex optimization are used to examine a model of the dopaminergic nerve terminal of the rat striatum. In the model, synthesis, storage, release, uptake, and metabolism are described by a set of non-linear differential equations. Parameters of the model are optimized with respect to diverse experimental data. These data include steady state passage of radioactivity, decline in total dopamine after synthesis inhibition, and change in extracellular dopamine concentration during electrical stimulation.

Animals↗
PubMed1987

Mechanisms contributing to the recovery of striatal releasable dopamine following MFB stimulation.

In vivo voltammetry was used to monitor the concentration of dopamine released into striatal extracellular fluid during electrical stimulation of the medial forebrain bundle of anesthetized rats. During stimulation the dopamine concentration increases rapidly to micromolar levels. After cessation of the stimulus, uptake mechanisms rapidly clear the released dopamine. That dopamine is the compound detected during stimulation is confirmed by voltammetry and pharmacology. The interval between stimulations influences the amount of dopamine released. When 10 s stimulations are spaced by 30 s, only 50% of the amount of dopamine released by the first stimulation is released by the second stimulation. Twenty minutes are required for full recovery of the stimulation response. Full recovery requires dopamine synthesis but during the initial 2 min following stimulation the recovery exceeds synthesis rates. Possible mechanisms that contribute to the rapid initial recovery are the mobilization of intraneuronally stored dopamine and the recycling of the released dopamine via presynaptic uptake mechanisms. Dopaminergic receptors are able to modulate the rapid recovery.

Animals↗
PubMed1987

Extracellular dopamine in rat striatum following uptake inhibition by cocaine, nomifensine and benztropine.

A microdialysis/smallbore chromatographic system was used to monitor changes in extracellular dopamine concentration in the striatum of the rat following administration of drugs that block catecholamine uptake. Analysis of 0.5 microliter of dialysate every 5 min showed dose-dependent elevations in extracellular dopamine following systemic administration of nomifensine (1 and 10 mg/kg), benztropine (5 and 25 mg/kg) and cocaine (3, 10 and 30 mg/kg). The order of potency in vivo was nomifensine greater than cocaine greater than benztropine. The short sampling interval allows accurate temporal profiles following pharmacological manipulations to be acquired.

Animals↗
PubMed1987

Detecting behaviorally relevant changes in extracellular dopamine with microdialysis.

A method is described for monitoring extracellular levels of striatal dopamine in the rat during behavior. The extracellular fluid is sampled using a microdialysis probe modified for use in behaving animals. Dopamine concentration in the perfusate is determined every 5 min using an automated smallbore chromatographic system with electrochemical detection. The system is capable of detecting behaviorally related changes of 5 nM, in extracellular dopamine.

Animals↗
PubMed1987

Dynamics of the recovery of releasable dopamine following electrical stimulation of the medial forebrain bundle.

In vivo voltammetry was used to monitor dopamine released into the extracellular fluid of the rat striatum by 10-s periods of electrical stimulation of nigrostriatal axons. By varying the interval between stimulations the dynamics of the recovery of the stimulation response has been investigated. The recovery is shown to be differentially affected by dopamine synthesis inhibition at short and long stimulation intervals. The recovery at less than 2 min is independent of dopamine synthesis. Processes in addition to dopamine synthesis must contribute to the recovery of the stimulation response.

Animals↗
PubMed1986

Striatal dopamine activity and unilateral barpressing in rats.

A micro-punch tissue assay was used to measure changes in dopamine content at twenty-six sites within the striatum of rats trained to barpress exclusively with one forepaw for food pellets. Analysis of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was carried out using HPLC with electrochemical detection. The barpress group had a significantly higher DOPAC/DA ratio in both the contralateral and ipsilateral hemispheres when compared to feeding and homecage controls. The DOPAC/DA ratio is considered to be a measure of dopaminergic neuronal activity, thus suggesting a bilateral activation of the neostriatal dopaminergic afferents as a result of the motor performance. Topographical analysis within the barpress group revealed an anterior-posterior, medial-lateral gradient of dopaminergic activity with the posterior and lateral sites showing the greatest increases over the controls. The results of this experiment indicate that localized changes in neuronal activity can be monitored with the micro-punch assay-HPLC/EC technique and that voluntary motor behavior produces an activation of the striatal dopamine system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Fatty acid composition of human erythrocyte membranes by capillary gas chromatography-mass spectrometry.

Capillary gas chromatographic and gas chromatographic--mass spectrometric methods were employed for profiling total fatty acid content of human erythrocyte membranes. The protocol was designed to efficiently separate, identify, and accurately quantify the fatty acid composition in human erythrocyte membranes. Washed erythrocyte "ghosts" were saponified in aqueous methanolic sodium hydroxide solution and methylated with boron trichloride and acid catalysis. Extracted total fatty acid methyl esters (FAMEs) were analyzed using a highly polar cyanopropylsiloxane SP 2560 fused-silica capillary column. Total run time was 55 min, and 45 FAMEs were tentatively identified by relative retention times compared to those of known FAMEs. Confirmation of identities by mass spectral structure elucidation revealed saturated, mono- and polyunsaturated, and branched-chain FAMEs. The presence of four fatty aldehydes was also confirmed as dimethyl acetal derivatives. Identification of cis/trans isomers was based on relative retention times and characteristic profile of the cis/trans FAME standard. Quantification of FAMEs for normal subjects showed some variation in relative amounts, consistent with expectations based on literature reports on total or phospholipid FAMEs from human erythrocytes. Separation of individual components of fatty acid families (n-3), (n-6), and (n-9) is demonstrated. Losses in relative amounts of polyunsaturated fatty acids upon storing samples were also detectable by this rapid method.

Chromatography, Gas↗
PubMed1985

Dopamine depletion in a striatal subregion disrupts performance of a skilled motor task in the rat.

Unilateral 6-hydroxydopamine injections into the lateral neostriatum disrupted the ability of rats to retrieve small food pellets with the contralateral forepaw. Similar injections into the medial striatum did not interfere with performance accuracy. Dopamine assays indicated that of the 5 striatal subregions analyzed, the lateral striatum at the level of the anterior commissure was most directly related to the behavioral deficit. The behavioral results are interpreted as providing evidence in support of a sensory role for the lateral striatal dopamine system.

Animals↗
PubMed1985

In vivo voltammetric determination of the kinetics of dopamine metabolism in the rat.

In vivo voltammetry at carbon paste electrodes placed in the striatum of chloral hydrate-anesthetized rats was used to monitor changes in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) following 1-min periods of electrical stimulation of the ascending nigro-striatal pathways. Statistical analysis of resultant changes in DOPAC allows simultaneous determination of the rate constants for the turnover of both dopamine (DA) (0.046/min) and DOPAC (0.053/min.). The data demonstrate that there are substantial temporal differences between neuronal release of DA and changes in striatal DOPAC levels. This should be considered when metabolite measurements are used as an index of neurotransmitter activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

A comparison of van't Hoff and calorimetric heats of binding to DNA using an ethidium selective electrode.

A liquid membrane electrode selective for ethidium ion was used to measure free ethidium in mixtures with calf thymus DNA. Electrode response was unaffected by variation in ionic strength from 1 mM to 0.5 M, and was not degraded over the temperature range studied. DNA-ethidium binding isotherms obtained with the electrode at 17.4, 25.4, 30.1, and 40.6 degrees C were fitted to a single class of excluded sites model for v ranging from 0.01 to 0.16. van't Hoff analysis of these data yielded delta H = -8300 cal/mol ethidium bound (in 0.5 M KCl, 10 mM Tris buffer, pH 10, 1 mM EDTA). Direct calorimetric measurements of the heat of complex formation led to a value of -7600 cal/mol at 25 degrees C in the same medium; the two results were not significantly different at the 95% confidence level. The agreement supports the validity of the ethidium selective electrode, and illustrates its utility in the study of ligand binding to nucleic acids and related materials.

Animals↗
PubMed1984

Neuroleptics increase striatal catecholamine metabolites but not ascorbic acid in dialyzed perfusate.

To determine the effects of dopamine receptor blockade upon oxidizable components of striatal extracellular fluid, high-performance liquid chromatography (HPLC) with electrochemical detection was used to assay levels of ascorbic acid, dihydroxyphenylacetic acid (DOPAC) homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in perfusates obtained from unanesthetized rats following i.p. administration of haloperiodol (1.0 mg/kg) or clozapine (20 mg/kg). Striatal push-pull perfusion was performed by passing artificial CSF between two pulled glass micropipets, encapsulated by a hollow, semipermeable cellulose fiber, thereby limiting recovery to compounds under mw 5000. Samples were directly injected into a C-18 column at half-hour intervals before and after neuroleptic administration. Haloperidol administration resulted in increases in extracellular DOPAC and HVA while failing to alter 5-HIAA or ascorbic acid levels. Similar results were found with clozapine, except for a more variable individual response to the drug; clozapine also produced a small increase in 5-HIAA levels. Animals given a saline injection did not show increases in any of these compounds. These data confirm the involvement of extracellular dopamine metabolites in the electrochemical signal increases observed in vivo following dopamine receptor blockade and provide evidence that extracellular ascorbic acid in the striatum is insensitive to peripheral neuroleptic administration.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Extracellular ascorbic acid increases in striatum following systemic amphetamine.

Push-pull perfusion of the anterior striatum was performed in freely moving rats which were administered 4 mg/kg d-amphetamine sulfate. Ascorbic acid was measured in the perfusate using high performance liquid chromatography with electrochemical detection. Increased extracellular ascorbic acid resulted from the amphetamine, lasting over a period of two hours. The time course of the increase corresponded to the increased oxidation current measured by intrastriatal chonoamperometry under equivalent conditions.

Animals↗