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Biomedical subjects

R H Roth

Publications and source records attributed to R H Roth.

At least 235 records · Page 13Linked to original sources
PubMed1981

The use of c8-octyl columns for the analysis of catecholamines by ion-pair reversed-phase liquid chromatography with amperometric detection.

The chromatographic behavior of norepinephrine (NE), epinephrine, dopamine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid on octylsilane (C8) reversed-phase high-performance liquid chromatography columns was observed under various mobile phase conditions including manipulations of pH, pairing ion and methanol concentrations. The optimum isocratic conditions permitting quantitative resolution of these substances in minimum time and with maximum detector response were determined. Employing a pH 3.0-3.2 mobile phase comprising an aqueous buffer solution containing 0.1 M NaH2PO4, 0.1 mM EDTA, and 0.2 mM 1-octanesulfonate, admixed with a volume of methanol equal to 4% of the aqueous volume, the performances of the C8 columns compares favorably to that of the more widely used C18 columns. The column eluates were monitored with an amperometric detector utilizing a glassy-carbon flow-cell electrode. The detector response for Ne was 1.5-2.0 nA/ng and the baseline noise was as little as 0.002 nA thereby permitting quantitation of 5-pg levels or more in the injected samples. By coupling the liquid chromatographic system to a procedure which eliminates non-catechol contaminants from the neuronal and body fluid specimens by alumina adsorption of the catechols, a sensitive and dependable method was developed and employed for the determination of catechol levels in discrete regions of rat brain, cat spinal cord, and in human plasma.

Animals↗
PubMed1981

Mesocortical dopamine neurons: rapid transmitter turnover compared to other brain catecholamine systems.

The decline of dopamine and norepinephrine after intravenous alpha-methyltyrosine was used to determine the rate constants for catecholamine turnover in the rat prefrontal cortex, olfactory tubercle and striatum. Dopamine turnover varied more between brain regions and was generally faster than the corresponding norepinephrine turnover. Prefrontal cortical dopamine was unaffected by dorsal noradrenergic bundle lesions. The turnover of prefrontal cortical dopamine was found to be 2-4 times faster than dopamine turnover in the olfactory tubercle and striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Brain contribution to the haloperidol-induced increase in plasma homovanillic acid.

Haloperidol increases the plasma concentration of the dopamine (DA) metabolite homovanillic acid (HVA). Since a substantial proportion of plasma HVA originates outside the brain, this effect could be due to a combination of both peripheral and central actions of haloperidol. In order to evaluate the relative contribution of central versus peripheral effects of haloperidol on plasma HVA, the effect of pretreatment with a peripheral monoamine oxidase inhibitor, debrisoquin, on the plasma HVA response to haloperidol was examined. In addition, the effect of haloperidol on plasma HVA was compared with that of domperidone, a peripheral DA receptor blocking agent. Debrisoquin pretreatment did not alter the haloperidol-induced increase in plasma HVA and domperidone had no effect on plasma HVA. Thus, the haloperidol effect on plasma HVA did not appear to be due to increased peripheral HVA production or blockade of peripheral DA receptor sites. It is concluded that the haloperidol-induced increase in plasma HVA is due largely or exclusively to the drug's action on the brain.

Animals↗
PubMed1981

Comparison of two alpha-noradrenergic agonists (clonidine and guanfacine) on norepinephrine turnover in the cortex of rats during morphine abstinence.

The effects of the alpha-agonists clonidine and guanfacine on rat cortical norepinephrine turnover during morphine withdrawal were assessed. Cortical norepinephrine levels were measured, after administration of alpha-methyl-p-tyrosine, by fluorometric assay. Chronic treatment with morphine did not affect norepinephrine levels or norepinephrine turnover. In control animals, doses up to 200 micrograms/kg clonidine and 1060 micrograms/kg guanfacine did not affect norepinephrine steady state levels, but did reduce alpha-methyl-p-tyrosine-induced norepinephrine depletion. As little as 5 micrograms/kg clonidine reversed the accelerated turnover observed during naloxone precipitated morphine withdrawal; while for guanfacine, the minimum effective dose was 212 micrograms/kg. the ED50 for guanfacine's reversal of the withdrawal-induced acceleration of turnover was approximately 60 times that for clonidine.

Adrenergic alpha-Agonists↗
PubMed1981

Apomorphine-haloperidol interactions: different types of antagonism in cortical and subcortical brain regions.

Apomorphine, a dopamine (DA) receptor stimulant induced a dose-dependent decrease in the content of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the olfactory tubercle and striatum of rats, but it was ineffective in the frontal cortex. Apomorphine also antagonized the haloperidol-induced accumulation of DOPAC and HAV in the olfactory tubercle and striatum, whereas in the frontal cortex it antagonized the effects of haloperidol on DOPAC but not on HVA. The total (free and conjugated) content of DA metabolites was measured in these experiments.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Presynaptic adrenergic receptor sensitivity in depression. The effect of long-term desipramine treatment.

Stimulation of presynaptic alpha 2-adrenergic receptors located on norepinephrine (NE)-containing cells in the brain decreases the firing rate and turnover of NE in these neurons. To assess whether abnormalities in the regulation of the NE system during desipramine hydrochloride treatment may be present in depressed patients, the effects of an alpha 2-agonist, clonidine hydrochloride, on plasma levels of the NE metabolite 3-methoxy-4-hydroxy/phenethyleneglycol (MHPG) and on blood pressure (BP) were evaluated in ten depressed patients before and during long-term desipramine treatment. Long-term desipramine treatment significantly attenuated the effects of clonidine on plasma MHPG level and BP, indicating that during desipramine treatment alpha 2-adrenergic receptors had become subsensitive. In addition, plasma MHPG levels were significantly reduced during long-term desipramine treatment. These findings are discussed in relation to the hypothesized therapeutic mechanism of action of desipramine and the hypotheses relating noradrenergic function and depression.

Adult↗
PubMed1981

Plasma MHPG in depression: effects of acute and chronic desipramine treatment.

The effects of acute and chronic desmethylimipramine (DMI) administration on 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in plasma and urine were examined in eight depressed inpatients. DMI treatment induced an immediate and continuous highly significant reduction in plasma MHPG throughout the 30-day treatment period. This effect was not related to treatment response. In contrast to plasma MHPG, there was no uniform effect of DMI treatment on urinary MHPG. Chronic DMI treatment increased or did not change urinary MHPG in the three treatment responders and decreased urinary MHPG in five nonresponders. The correlation between plasma and urinary MHPG during the placebo period was not significant, and the effect of DMI treatment on the two measures differed markedly.

Adult↗
PubMed1981

Gamma-hydroxybutyrate treatment of schizophrenia: a pilot study.

Gamma-hydroxybutyrate (GHB) was administered to seven chronic schizophrenic patients in the first double-blind, placebo-replacement trial of this compound. No significant drug effect in this group was obtained. Two patients became nonpsychotic during the drug trial, three got worse and two patients did not respond. The two patients who responded with improvement were augmenters, as measured by average evoked potential (EP), had low platelet MAO activity and high cerebrospinal fluid (CSF) homovanillic acid (HVA). A number of patients developed akathisia and dystonia during the trial, especially after receiving probenecid for lumbar puncture. Further study is warranted, possibly in a selected patient group.

Double-Blind Method↗
PubMed1981

High-affinity [3H]choline accumulation in cultured human skin fibroblasts.

[3H]Choline can be transported across cell membranes by high-affinity (KT less than 5 microM) and low-affinity (KT much greater than 5 microM) systems. High-affinity choline accumulation (HACA) has been demonstrated in synaptosomes made from cholinergic brain regions such as the hippocampus and caudate-putamen. In cell culture, HACA has been demonstrated in glia and avian telencephalon, dissociated spinal cord, and muscle fibroblasts. We examined [3H]choline accumulation in a single normal human fibroblast line cultured from skin biopsy. [3H]Choline accumulation was temperature-dependent and linear with incubation time up to 6 min at 0.125 microM-choline. The apparent KT for [3H]choline was 5 microM, which is similar to that observed in avian fibroblasts. Isoosmotic replacement of Na+ with either Li+ (144 mM) or sucrose (288 mM) severely reduced [3H]choline accumulation (by 70-90%). Pre-incubation with ouabain (100 microM), sodium orthovanadate (100 microM), or 2,4-dinitrophenol (100 microM), or replacement of Ca2+ by Mg2+ had little or no effect on subsequent [3H]choline accumulation. [3H]Choline accumulation was inhibited by hemicholinium-3 (HC-3); after pre-incubation in HC-3 at 37 degrees C for 10 min, the IC50 (at 0.125 microM-choline) was 5.6 microM. The HC-3 sensitivity, Na+ dependence, and low KT suggest that human skin fibroblasts have a high-affinity transport system for choline.

Adult↗
PubMed1981

Increased noradrenergic metabolism in the cerebellum of the mouse mutant dystonia musculorum.

The neurological mouse mutant dystonia musculorum exhibits bizarre appendicular and truncal dystonia without known cerebellar histopathology. We evaluated striatal dopamine and cerebellar norepinephrine metabolism in this mutant and compared the results with those obtained in wild-type BALB/c and B6C3 controls. Tyrosine hydroxylase activity and dopamine metabolite levels (homovanillic acid and 3,4-dihydroxyphenylacetic acid) in the striatum of the mutant were similar to controls. Tyrosine hydroxylase activity and the steady-state level of 3-methoxy-4-hydroxyphenethyleneglycol, a metabolite of norepinephrine, in the cerebellum were 38% and 42-66%, respectively, greater in the mutant. However, the level of norepinephrine was similar (approximately 350 ng/g). Further, a Purkinje cell-specific marker, cGMP-dependent protein kinase, was unchanged in the mutant and no Purkinje cell pathology was observed with light microscopy. The lack of Purkinje cell derangement and similar levels of cerebellar norepinephrine and cGMP-dependent protein kinase activity suggest that increased norepinephrine metabolism in the cerebellum of this mutant is not a morphological response to gross target cell loss during morphogenesis. The observed changes may be a reaction to abnormal impulse traffic or altered input/output pathways to the mutant cerebellum during its development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Cerebrospinal fluid GABA and cyclic nucleotides in alcoholics with and without seizures.

Cerebrospinal fluid levels of gamma-aminobutyric acid (GABA) and cyclic nucleotides were measured in alcoholic and control patients. Alcoholics without seizures had higher GABA levels than either alcoholics with seizures or controls. Levels of cyclic AMP and cyclic GMP in cerebrospinal fluid of controls and alcoholics with and without seizures were not significantly different.

Alcoholism↗
PubMed1981

Intrastriatal kainic acid: acute effects on electrophysiological and biochemical measures of nigrostriatal dopaminergic activity.

The acute effects of intrastriatal kainic acid injection in nigrostriatal dopamine cell activity were assessed using electrophysiological and biochemical techniques. One hour after kainic acid injection, dopamine cell firing rates were significantly increased, as were striatal dopamine synthesis (dopa accumulation) and dopamine metabolism (3,4-dihydroxyphenylacetic acid levels). Twelve hours postkainic acid administration, cell firing rate had returned to control levels, as had dopa accumulation and DOPAC levels, but the number of dopamine cells firing had significantly decreased. Action potentials were elicited from the "silent" dopamine cells by iontophoretic application of gamma-aminobutyric acid but not glutamate. Conversely, 48 hr after kainic acid, the number of dopamine cells firing was significantly increased, as were 3,4-dihydroxyphenylacetic acid levels. Both cell firing rate and dopa accumulation, however, matched control values. The results are discussed in terms of the role of strionigral pathways in mediating the acute effects of kainic acid on the nigrostriatal dopaminergic system and are interpreted in light of the recently described phenomenon of presumed dopamine cell depolarization inactivation.

Animals↗