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B Moghaddam

Publications and source records attributed to B Moghaddam.

50 records · Page 3Linked to original sources

Effect of L-glutamate on the release of striatal dopamine: in vivo dialysis and electrochemical studies.

Microdialysis and in vivo voltammetry combined with K(+)-selective microelectrodes were utilized to study the effect of L-glutamate (GLU) on the in vivo release of dopamine (DA) from the rat striatum. Perfusion of 500 nM-5 mM GLU through the microdialysis probe was without an effect on DA outflow whereas 10 mM GLU resulted in a significant (295%) increase in the basal level of DA. This increase was blocked in the presence of 2-amino-5-phosphonopentanoic acid, an N-Methyl-D-aspartate (NMDA) receptor antagonist. Repetitive local applications of 10 mM GLU were also required to observe an increase in extracellular DA measured by in vivo voltammetry. These signals were accompanied with a massive increase in extracellular K+ and a large negative shift in the field potential resembling the ionic changes seen after the phenomenon spreading depression. These studies suggest that high concentrations of GLU are required to enhance the extracellular concentration of DA in vivo. Further, pathophysiological conditions such as spreading depression may be responsible for the observed increase in extracellular DA concentration.

Animals↗

Utilization of microdialysis for assessing the release of mesotelencephalic dopamine following clozapine and other antipsychotic drugs.

1. In vivo microdialysis was utilized to assess the effect of clozapine, haloperidol, and sulpiride on the release of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. 2. The results suggest that acute administration of various classes of antipsychotic drugs may differentially increase the extracellular concentration of dopamine in mesotelencephalic systems. Haloperidol and sulpiride were more effective in releasing dopamine from the terminals of the nigrostriatal dopamine system while clozapine had a more prefrontal effect on the mesolimbic and particularly the mesocortical dopamine systems.

Animals↗

Characterization of dopamine release in the rat medial prefrontal cortex as assessed by in vivo microdialysis: comparison to the striatum.

Using the technique of perfusion microdialysis combined with a small-bore liquid chromatography system we have measured the basal and drug-induced fluxes of extracellular dopamine in the medial prefrontal cortex of chloral hydrate-anesthetized rats and have compared our findings in the cortex to that observed in the striatum. The results were as follows. (1) At a flow rate of 2 microliter/min, the basal level of dopamine in the medial prefrontal cortex was 0.28 +/- 0.1 (n = 32) fmol/microliter perfusate, which was nearly an order of magnitude less than that obtained from the striatum. (2) alpha-Methyl-para-tyrosine (150 mg/kg i.v.) significantly decreased the extracellular levels of striatal and cortical dopamine. The magnitude and duration of the responses were similar in both regions. (3) Local perfusion with 30 mM K+ had a more profound effect on dopamine release in the striatum than in the medial prefrontal cortex. The K(+)-induced release in both regions was significantly attenuated in the absence of Ca2+. (4) The anxiogenic beta carboline FG 7142 (15 mg/kg, i.p.) enhanced the release of cortical dopamine by about 50% while it was without an effect in the striatum. (5) Amphetamine (1 mg/kg, i.v.) significantly elevated, while reserpine (5 mg/kg, i.p.) rapidly attenuated, the dopamine level in the medial prefrontal cortex. These studies demonstrate that perfusion microdialysis, in conjunction with small-bore liquid chromatography with electrochemical detection, can be used to measure the basal release of dopamine in the rat medial prefrontal cortex and that the dopamine release process in this region, as has been shown in the striatum, is sensitive to stimulation conditions and pharmacological manipulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study.

In vivo microdialysis has been used to study the acute effects of antipsychotic drugs on the extracellular level of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. (-)-Sulpiride (20, 50, and 100 mg/kg i.v.) and haloperidol (0.1 and 0.5 mg/kg i.v.) enhanced the outflow of dopamine in the striatum and nucleus accumbens. In the medial prefrontal cortex, (-)-sulpiride at all doses tested did not significantly affect the extracellular level of dopamine. The effect of haloperidol was also attenuated in the medial prefrontal cortex; 0.1 mg/kg did not increase the outflow of dopamine and the effect of 0.5 mg/kg haloperidol was of shorter duration in the prefrontal cortex than that observed in striatum and nucleus accumbens. The atypical antipsychotic drug clozapine (5 and 10 mg/kg) increased the extracellular concentration of dopamine in all three regions. In contrast to the effects of sulpiride and haloperidol, that of clozapine in the medial prefrontal cortex was profound. These data suggest that different classes of antipsychotic drugs may have distinct effects on the release of dopamine from the nigrostriatal, mesolimbic, and mesocortical terminals.

Animals↗

Differential effect of cocaine on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens: comparison to amphetamine.

The technique of in vivo microdialysis was used to measure the extracellular levels of dopamine in the nucleus accumbens septi and medial prefrontal cortex of chloral-hydrate-anaesthetized rats following systemic administration of cocaine and amphetamine. Intravenous injection of cocaine increased the extracellular levels of dopamine in the medial prefrontal cortex and the nucleus accumbens septi in a dose-dependent manner. However, the magnitude of increase was significantly greater in nucleus accumbens than in medial prefrontal cortex. In comparison to cocaine, amphetamine increased the extracellular levels of dopamine in the nucleus accumbens and medial prefrontal cortex to the same degree. Based on the relatively small increase of extracellular dopamine levels in medial prefrontal cortex by cocaine, it is postulated that dopaminergic innervation of other structures besides medial prefrontal cortex may be involved in maintenance of cocaine self-administration.

Amphetamines↗

Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine.

While using the technique of in vivo microdialysis, we have assessed the effect of the ionic composition of the perfusing solution on extracellular dopamine levels during resting conditions and following a pharmacological manipulation. Our results indicate that perfusion with solutions containing the ionic composition of commercially available Ringer's solution, which mimic the ionic composition of plasma as opposed to brain extracellular fluid, alters the turnover rate and basal release of dopamine. Moreover, perfusion with solutions containing higher calcium levels, i.e., 3.4 mM, than the amount we have determined to be present in the extracellular fluid of striatum (1.2 mM) alters the pharmacological responsiveness of the nigrostriatal dopamine system to synthesis inhibition.

Animals↗

Regional differences in resting extracellular potassium levels of rat brain.

The extracellular potassium concentration in the cerebral cortex of the mammalian brain has been repeatedly reported to be approximately 3.0 mM. We have made detailed measurements with potassium-selective microelectrodes and have found significantly lower extracellular potassium concentrations in unstimulated rat brain caudate and thalamus (1.9-2.5 mM) when compared to cortex and cerebral spinal fluid (3.0-3.5 mM). These regional differences may be caused by variations in spontaneous activity of neurons, regional permeability differences in endothelial cells of brain capillaries to potassium, or caused by variations in uptake by glia.

Animals↗

Electrocoating carbon fiber microelectrodes with Nafion improves selectivity for electroactive neurotransmitters.

A method which improves carbon fiber microelectrode selectivity for cationic amines by electrocoating the fiber with a thin film of the ionic polymer, Nafion, is described. The selectivity and response speed of these electrodes for the detection of electroactive cationic and anionic species found in brain extracellular fluid was evaluated using differential pulse voltammetry and chronoamperometry and compared to uncoated fibers. Carbon fiber microelectrodes electrocoated with Nafion are highly sensitive to cationic amines such as dopamine and serotonin and have minimal sensitivity to anions such as ascorbic acid and uric acid at physiological concentrations.

Carbon↗

Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia.

Brain ion homeostasis is severely perturbed during spreading depression of Leao and during anoxia. The ionic composition of the extracellular space changes abruptly and approaches the intracellular concentrations owing to an increase in cell permeability. In spreading depression, synchronous transmitter efflux caused by a depolarization of the presynaptic terminals has been implicated as a possible mechanism that would explain the concomitant movement of ions. Anoxia, having many features in common with spreading depression, may follow the same mechanism. We have measured the concentrations of extracellular potassium with ion-selective microelectrodes and dopamine by in vivo voltammetry with carbon fiber microelectrodes during spreading depression and anoxia to compare the temporal relationship between the release of dopamine and ion movements in the striatum. There is a pronounced release of dopamine during both spreading depression and anoxia. In spreading depression, the sharp increase of potassium concentration that follows an initial smaller and slower increase of potassium is accompanied by the release of dopamine. In anoxia, the dopamine release clearly precedes the fast rise of extracellular potassium concentration. We conclude that in striatum, there is a pronounced dopamine release during spreading depression and anoxia, but that the relationships between ionic changes and transmitter release for these two phenomena are different and probably reflect different mechanisms.

Animals↗

Simultaneous monitoring of voltammetric and ion-selective electrodes in mammalian brain.

A new technique of simultaneously recording from ion-selective and voltammetric microelectrodes in vivo allows one to measure concomitant ionic and monoamine neurotransmitter fluxes in the extracellular fluid space of the brain. Examples are presented of the results obtained with various drug and stimulus applications. The time correlations of the ionic and neurotransmitter fluxes are especially useful in attempting to better understand the possible interactions of these chemical dynamics with neuronal functioning.

Animals↗

Nafion-coated electrodes with high selectivity for CNS electrochemistry.

A major improvement in the selectivity of small graphite electrodes used for in vivo electrochemistry is described. The electrodes are coated with Nafion, a perfluorosulfonated polymer. This coating is practically impermeable to ascorbic acid and anionic biogenic amine metabolites and only slightly responsive to neutral metabolites. Thus it becomes selective for the cationic primary neurotransmitters, dopamine, norepinephrine and 5-hydroxytryptamine. Responses of Nafion-coated and untreated electrodes in vivo are compared.

Animals↗

Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia.

The mechanisms which contribute to the actions of atypical antipsychotic drugs, such as clozapine and the putative atypical agents remoxipride and raclopride, are reviewed. Examination of available preclinical and clinical data leads to two hypotheses concerning the mode of action of atypical antipsychotic drugs. The first hypothesis is that antagonism of the dopamine D2 receptor is both necessary and sufficient for the atypical profile, but that interaction with subtypes of the D2 receptor differentiates typical from atypical antipsychotic drugs. The second hypothesis has been previously advanced, and suggests that a relatively high ratio of serotonin 5-HT2:dopamine D2 receptor antagonism may subserve the atypical profile. It seems likely that the atypical antipsychotic drug profile may be achieved in more than one way.

Antipsychotic Agents↗