Search PubMed⌕ Search

Biomedical subjects

G A Gerhardt

Publications and source records attributed to G A Gerhardt.

At least 109 records · Page 6Linked to original sources
PubMed1990

Multichannel semiconductor-based electrodes for in vivo electrochemical and electrophysiological studies in rat CNS.

Five-channel silicon-based microprobes were sputter-coated with carbon, coated with Nafion, and used for both in vivo electrochemical and single-unit electrophysiological recordings. High-speed electrochemical studies were performed in vitro and in vivo, which demonstrated that these multisite probes were capable of monitoring the evoked overflow of monoamines in selected brain regions of the rat. In addition, action potentials from Purkinje cells in the rat cerebellum, identified electrophysiologically, were recorded from different sites on the same probe. Spontaneous firing rates could be monitored for up to 2 hours in order to investigate the effects of systemic administration of phencyclidine. These results provide preliminary evidence that solid-state multi-site probes can be utilized for both in vivo electrochemical and electrophysiological studies in the rat brain.

Animals↗
PubMed1990

Combined electrochemical and electrophysiological studies of monoamine overflow in rat hippocampal slices.

In vivo electrochemical measurements of chronoamperometric recordings from Nafion-coated electrodes were used to investigate monoamine overflow from selected regions of the rat hippocampal slice. Concurrent electrophysiological measurements of evoked CA1 pyramidal cell population spike responses were used to characterize changes in the electrical activity in the slices that occur during potassium-induced neurotransmitter overflow. Superfusion with elevated K+ (10-50 mM, 5 min) elicited consistent concentration-dependent increases in the electrochemical responses recorded from the dentate gyrus. At the onset of K+ perfusion, there was an initial increase in the population spike response, followed by electrical silence, which usually lasted 5-10 min following the return to normal medium, and required 20-30 min for complete recovery of the response. The potassium-induced electrochemical signal always increased following the decline in the electrophysiological response. Although the electrochemical signal usually returned to baseline much before the electrophysiological response (usually within 5 min), both signals remained refractory for some time. Cocaine pretreatment (10-50 microM) caused a dose-dependent augmentation of the electrochemical responses. Local pressure ejection of K+ via a micropipette elicited dose-dependent increases in the electrochemical signals that were of relativity brief duration as compared to superfusion with K+. Such potassium-evoked responses were highly localized, and were attenuated in amplitude in animals that had been previously treated with the selective noradrenergic neurotoxin, DSP-4. In addition to K+, local applications of methyl-amphetamine, tyramine and veratridine also elicited electrochemical signals, and the time courses of these responses were specific to the releasing agent that was used. Preliminary data obtained using high-speed electrochemical recordings of both oxidation and reduction current suggested that tyramine ejections evoked primarily norepinephrine overflow, while K+ evoked the overflow of both norepinephrine and serotonin. The present experiments demonstrate that simultaneous electrophysiological and electrochemical experiments can be used in an isolated preparation of brain such as the hippocampal slice to characterize the electrophysiological events that occur during stimulated transmitter release.

Animals↗
PubMed1990

Electrochemical characterization of stimulated norepinephrine overflow in locus coeruleus-hippocampus double brain grafts grown in oculo.

Rat locus coeruleus-hippocampus double in oculo brain grafts were studied with high-speed electrochemical techniques to characterize stimulus-evoked overflow of norepinephrine. Local pressure ejections of KCl into the locus coeruleus (LC) portion of the double graft elicited electrochemical signals in the hippocampal portion that had NE-like reduction/oxidation current ratios. In contrast, electrical stimulation of the LC part of the double graft did not lead to consistently detectable signals in the hippocampal portion of the transplant. These data demonstrate that LC graft neurons are able to release NE in target tissues when stimulated in an appropriate manner, and that the time course and magnitude of the overflow of NE can be detected with sensitive high-speed electrochemical recording techniques.

Animals↗
PubMed1990

Sensory gating deficits in psychiatric inpatients: relation to catecholamine metabolites in different diagnostic groups.

Acutely ill psychiatric inpatients were examined for a deficit in sensory gating, measured as failure to suppress the P50 wave of the auditory-evoked response to the second of paired stimuli. Previously, we had found that in mania, this sensory gating deficit is correlated with increased plasma-free levels of the noradrenergic metabolite 3-methoxy, 4-hydroxyphenylglycol (pMHPG), whereas in schizophrenia, there is no correlation with catecholamine metabolism. To assess the generalizability of these findings, we examined inpatients with a broader range of diagnoses, including those with multiple DSM III-R Axis I, II, and III diagnoses. The patients were grouped into three diagnostic spectra for analysis: schizophrenic, manic, and depressive. In the schizophrenic patients, there was no relationship between pMHPG or other catecholamine metabolites and the sensory gating deficit. In manic patients, however, a positive correlation between pMHPG level and the sensory gating deficit was again observed. This relationship did not extend to the depressive patients, who uniquely showed sensory gating deficits that correlated negatively with the severity of their illness. The data suggest that sensory gating deficits are common to these three diagnostic spectra, but the deficits in each group have different relationships to catecholamine metabolism and symptom severity that may reflect differences in the underlying neuronal pathophysiology of these illnesses.

Adult↗
PubMed1990

Regulation of adrenergic receptors in intraocular hippocampal transplants: role of noradrenergic innervation.

Hippocampal tissue transplanted into the anterior chamber of the eye offers a unique system in which development can be studied in the absence of the noradrenergic innervation. This system was used to determine the extent to which noradrenergic innervation regulates the development of adrenergic receptors. In addition to examining single denervated transplants, transplants grown with innervation from the superior cervical ganglia of the host rat or from locus coeruleus cotransplants were also examined to determine whether the source of norepinephrine and extent of innervation in oculo regulate the development and density of adrenergic receptors. In vitro autoradiographic analysis of ligand binding to both alpha 1- and beta-adrenergic receptors with 125I-BE 2254 and 125I-pindolol, respectively, was used to characterize adrenergic receptors in the intraocular transplants. Quantitative analysis of the receptors showed an up-regulation of both alpha 1- and beta-adrenergic receptors in tissue grown in the absence of norepinephrine, but in general there was not a high degree of correlation between norepinephrine content and receptor density. Although high-performance liquid chromatography (HPLC) analysis of catecholamines revealed higher than normal amounts of norepinephrine in hippocampal transplants innervated by the superior cervical ganglia or a locus coeruleus cotransplant, the density of alpha 1 and beta receptors was quite comparable with values found in the literature for normal adult hippocampus. These results suggest that the relationship between receptor number and density of innervation may differ significantly from what is observed in response to pharmacological manipulation of norepinephrine systems in the adult brain.

Adrenergic alpha-Antagonists↗
PubMed1990

Effect of chronic caffeine administration on monoamine and monoamine metabolite concentrations in rat brain.

Caffeine was chronically administered in four doses (0, 10, 25, and 50 mg/kg/day) to rats via twice-daily intraperitoneal injections for 30 days. Concentrations of brain tissue monoamines, dopamine (DA), norepinephrine (NE), and serotonin (5HT), and monoamine metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5HIAA), were determined. At the 10 mg/kg/day dose, no significant changes were found compared with controls. At 25 mg/kg/day and 50 mg/kg/day significant changes were observed within each monoamine system. In striatum, DA and 5HT were increased, while DOPAC was decreased. In frontal cortex, NE was increased. In cerebellum, 5HT and MHPG were increased.

Animals↗
PubMed1990

Sensory physiology and catecholamines in schizophrenia and mania.

Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment.

Adult↗
PubMed1989

The effects of cholecystokinin (CCK-8) on dopamine-containing nerve terminals in the caudate nucleus and nucleus accumbens of the anesthetized rat: an in vivo electrochemical study.

The action of cholecystokinin (CCK) on presynaptic function of dopaminergic nerve terminals has been the subject of much debate in the literature. In efforts to resolve some of the reported ambiguities, high speed in vivo electrochemical recordings were carried out in the caudate nucleus and nucleus accumbens of the urethane anesthetized rat, to determine effects of locally applied sulfated (CCK-8S) and unsulfated (CCK-8US) CCK octapeptide. Locally-applied CCK-8S and CCK-8US caused no increase in the baseline electrochemical signals recorded from either brain region. However, locally applied CCK-8S potentiated the potassium-evoked overflow of dopamine (DA) into the extracellular space in both the caudate and nucleus accumbens. In contrast, pressure ejection of CCK-8US produced no significant effects on the potassium-evoked overflow of DA in either structure. These data support a facilitatory effect of CCK-8S on potassium-evoked overflow from DA-containing nerve terminals in the urethane anesthetized rat that is likely mediated through a peripheral type CCK receptor.

Anesthesia↗
PubMed1989

Direct determination of unconjugated HVA in human plasma filtrates by HPLC coupled with dual-electrode coulometric electrochemical detection.

We report a procedure for the rapid determination of unconjugated homovanillic acid (HVA) in human plasma by cartridge filtration followed by direct injection into an isocratic HPLC system coupled with dual-electrode coulometric electrochemical detection. Sample preparation is rapid and more than 72 samples can be studied in 24 h using an automated HPLC system. The intra- and interassay precisions of the assay equal or exceed previously reported methods. While this methodology has been employed to study plasma free HVA, the concept of the technique may be applicable to other compounds, as well as different assay procedures, to greatly decrease sample preparation time.

Autoanalysis↗
PubMed1989

Unconjugated methoxylated catecholamine metabolites in human saliva. Quantitation methodology and comparison with plasma levels.

A newly developed method for the simultaneous extraction and quantitation of the unconjugated levels of the catecholamine metabolites vanilmandelic acid (VMA), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and homovanillic acid (HVA) in plasma by high performance liquid chromatography with electrochemical detection was modified and applied to studies of human saliva. The assay had a mean coefficient of variation under 3% for each of the metabolites. Levels of plasma VMA, MHPG and HVA were measured in 28 normal subjects and compared to their saliva levels, obtained before and after stimulation by mastication. Significant correlations were found between plasma and saliva MHPG and HVA, but there was no correlation between plasma and saliva VMA. Salivary MHPG and HVA can be reproducibly assayed and may be useful tools for indications of changes in central and peripheral catecholamine metabolism.

Catecholamines↗
PubMed1989

Human ventral mesencephalic xenografts to the catecholamine-depleted striata of athymic rats: ultrastructure and immunocytochemistry.

On the basis of animal studies, grafts of fetal human dopaminergic cells have been suggested as a therapy for Parkinson's disease. The purpose of this study was to characterize the ultrastructure and immunocytochemistry of human ventral mesencephalic xenografts placed into the catecholamine-depleted striata of athymic "nude" rats. Human fetal tissue was obtained from tissue fragments derived from elective abortions during the first trimester of pregnancy. Small pieces of the basal mesencephalon were grafted into the catecholamine-depleted striata of four athymic nude rats. The rats were allowed to survive from 3 to 6 months after grafting; following fixation, the striatal tissue containing the grafts was labeled with antibodies against tyrosine hydroxylase and serotonin. Immunocytochemistry revealed tyrosine-hydroxylase-like-immunoreactive (THLI) and serotoninlike-immunoreactive (5HTLI) cell bodies within the human grafts. Both 5HTLI and THLI fibers crossed the graft-host interface and innervated the previously lesioned striatum. Both types of fibers also entered the host cortex from the adjacent human graft. At the ultrastructural level, THLI and 5HTLI fibers and synaptic terminals were observed in the host neuropil. THLI and 5HTLI dendrites and axon terminals were also observed in the neuropil of the grafts themselves. THLI axon terminals are not normally present in the substantia nigra. The results of our study indicate that human xenografts can survive in the neuropil of the host striatum and form morphologically appropriate synapses within the host brain.

Animals↗
PubMed1989

Outflow and overflow of picogram levels of endogenous dopamine and DOPAC from rat striatal slices: improved methodology for studies of stimulus-evoked release and metabolism.

An improved method for the rapid and sensitive determination of endogenous dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in superfusates of single rat striatal slices, using high-performance liquid chromatography (HPLC) coupled with 'coulometric' electrochemical detection (EC), is described. Superfusates are directly injected into an HPLC-EC system following addition of a small aliquot of solubilized ascorbate-oxidase. DA and DOPAC are both separated and quantitated in 3-5 min. Twelve to 15 samples can be analyzed each hour with a nominal detection limit of 1.0 pg per injection for each compound or 10-20 pg/ml of superfusate. The present method was used to study changes in DA and DOPAC outflow and overflow in superfusates of single striatal slices following electrical field stimulation, both in the absence and presence of the catecholamine uptake inhibitor nomifensine. Studies of 1 min superfusate collections clearly showed that electrical field stimulation produced a latent increase in DOPAC as compared to DA. The routine sensitivity and sample throughout of the method allows for studies of both outflow and overflow of DA and DOPAC, as well as studies involving time-dependent overflow of these compounds.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

In vivo electrochemical studies of monoamine release in the medial prefrontal cortex of the rat.

The magnitude and duration of release of monoamines evoked by local applications of potassium were measured in vivo in the medial prefrontal cortex using high-speed chronoamperometry. Typical electrochemical signals reflecting released of electroactive species ranging from 0.5 to 3.0 microM and lasting 90-120 s were detected at a variety of dorsal-ventral and anterior-posterior electrode placements in the medial prefrontal cortex. The magnitude of the reduction current measured following the oxidation reaction suggests a contribution of both serotonin and dopamine to the electrochemical signal, dopamine serving as the predominant monoamine in the medial prefrontal cortex proper and serotonin appearing to predominant in the more posterior regions of the frontal cortex. This conclusion was reinforced by the fact that unilateral 6-hydroxydopamine lesions of ascending dopamine fibers almost completely abolished electrochemical signals in the ipsilateral but not in the contralateral medial prefrontal cortex. The present study provides an in vivo characterization of monoamine release in the mesocortical dopamine terminal field, where it has been suggested that psychomotor stimulants may produce some of their positive reinforcing effects.

Dopamine↗
PubMed1988

The effects of delta 9-tetrahydrocannabinol on potassium-evoked release of dopamine in the rat caudate nucleus: an in vivo electrochemical and in vivo microdialysis study.

The effect of systemically administered delta 9-tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, on the potassium-evoked release of dopamine (DA) was examined in the neostriatum of the chloral hydrate anesthetized rat. Both in vivo electrochemical and in vivo microdialysis techniques were employed. A low dose of THC (0.5 mg/kg, i.p.) increased the time course of potassium-evoked in vivo electrochemical signals corresponding to released extracellular DA. In vivo microdialysis showed an increase in potassium-evoked DA release following 0.5 and 2.0 mg/kg doses of THC. Potassium-evoked electrochemical signals corresponding to released extracellular DA were augmented in time course following i.p. administration (5.0 mg/kg) of nomifensine, a recognized and potent catecholaminergic reuptake blocker. In addition, in vivo brain microdialysis studies of nomifensine (5.0 mg/kg i.p.) on neostriatal potassium-evoked DA release showed that DA levels were augmented in magnitude over the time course of the microdialysis. Taken together, these studies indicate that THC has a potent presynaptic augmenting effect on at least the neostriatal portions of the mesotelencephalic DA system in the rat, although the possibility that this effect could be mediated transsynaptically cannot be ruled out. Given the previous extensive evidence for an involvement of portions of the mesotelencephalic DA system in mediating the reinforcing and euphorigenic properties of many classes of abused drugs, and in mediating direct electrical brain stimulation reward, we suggest that the presently demonstrated effects of THC on forebrain dopamine function may be related to marijuana's euphorigenic properties and, thus, to its abuse potential.

Caudate Nucleus↗
PubMed1988

Toluene exposure during maturation of intraocular brain tissue transplants: alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine.

The effects of chronic toluene exposure on central neurons were examined using syngeneic grafts into the anterior chamber of the eye. Young adult albino rats with intraocular brain transplants inhaled toluene (1000 ppm) for 9 weeks starting at the time of transplantation, or from Week 8 to 17 after the graft was placed in oculo. Control animals were exposed to room air during the same intervals. Toluene treatment during development did not affect general growth or morphology of any of the brain areas examined. The distribution of neurofilament or glial fibrillary acidic protein immunoreactivity was similar in the experimental group and control group as well. Extracellular recordings of cerebellar Purkinje neurons showed a significantly reduced spontaneous firing rate, of 15-25%, both in intraocular transplants and in cerebellum in situ in toluene exposed animals. Postsynaptic sensitivity of intraocular and in situ Purkinje neurons to norepinephrine (NE) was evaluated. Purkinje neurons in transplants exposed to toluene during development were markedly supersensitive to superfused NE as compared to controls, while neither Purkinje neurons in mature cerebellar grafts nor cerebellum in situ showed any effects of the toluene treatment on NE sensitivity. The tissue content of NE in transplants exposed to toluene during maturation, evaluated with high-performance liquid chromatography coupled with electrochemical detection, was greater than that in the control grafts. Moreover, the content of free (3-methoxy-4-hydroxyphenyl) ethylene glycol (MHPG) was increased in both transplant and host cerebellum after toluene exposure. Taken together, these data indicate that toluene exposure during development of cerebellar grafts in oculo causes changes in postsynaptic noradrenergic sensitivity as well as decreased spontaneous activity of Purkinje neurons. Toluene exposure of adult cerebellum in situ or in oculo appears to decrease the Purkinje neuron discharge rate and increase NE turnover, but has no marked effect on postsynaptic NE sensitivity.

Administration, Inhalation↗
PubMed1988

Potentiation of morphine-elicited circling by dopaminergic uptake blockade.

Contraversive circling induced by unilateral infusions of morphine (7.5 nanomoles or 5 micrograms) into the ventral tegmental area was studied under conditions of dopamine uptake inhibition. Dopamine uptake blockade with either nomifensine (2.5 mg/kg) or GBR 13069 (2.0 mg/kg) resulted in a 3-fold increase in the rate of circling. Naloxone (1.5 mg/kg) attenuated but did not completely block the potentiated circling. These data are consistent with the hypothesis that morphine causes contraversive circling through local activation or disinhibition of dopaminergic cell firing.

Animals↗
PubMed1988

Effects of electrical stimulation of brain reward sites on release of dopamine in rat: an in vivo electrochemical study.

Behavioral studies suggest that mesencephalic dopamine neurons mediate the rewarding effects of electrical stimulation of the medial forebrain bundle. Yet there is little direct evidence that rewarding electrical stimulation actually activates dopamine-containing neurons. The purpose of the present study was to determine, using in vivo electrochemistry, if electrical stimulation applied to lateral hypothalamic or ventral tegmental reward sites would elicit changes in extracellular levels of dopamine. In vivo high speed chronoamperometric recordings were performed in anesthetized rats that had been previously trained to respond for rewarding electrical stimulation of the medial forebrain bundle or ventral tegmental area. We found that a single 500 msec train of pulses elicited a small transient electrochemical signal, the magnitude of which was dependent on the pulse duration and frequency. This signal was potentiated by inhibition of dopamine reuptake. Prolonged electrical activation with a self-stimulation-like regimen resulted in the gradual accumulation of an electroactive compound, tentatively identified as dihydroxyphenylacetic acid (DOPAC). Taken together, the data reported here support the idea that rewarding electrical stimulation causes the release of dopamine.

Animals↗