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Biomedical subjects

R H Roth

Publications and source records attributed to R H Roth.

At least 307 records · Page 17Linked to original sources
PubMed1977

Dihydroxyphenylacetic acid conjugate: natural occurrence and demonstration of probenecid-induced accumulation in rat striatum, olfactory tubercles and frontal cortex.

Methods for the synthesis of 14C-dihydroxyphenylacetic acid (DOPAC) conjugate and for the fluorometric determination of both free and conjugated DOPAC in the same tissue sample are described. Both free and conjugated DOPAC were demonstrated to occur endogenously in the rat corpus striatum, olfactoy tubercles and frontal cortical area, and the ratio of conjugated DOPAC to free DOPAC was 2-3 times greater in the olfactory tubercles and frontal cortical area than in the striatum. Probenecid administration (200 mg/kg, i.p., 4 and 2h before sacrificing) significantly increased the levels of DOPAC conjugate in all 3 brain areas studied. The levels of free DOPAC were also increased in the olfactory tubercles and frontal cortex by the probenecid treatment, but this increase was much less than that seen for DOPAC conjugate in these regions. Free DOPAC levels in the striatum were unaffected by the probenecid treatment. In all 3 brain areas studied, therefore, probenecid treatment resulted in a significant accumulation of conjugated DOPAC relative to free DOPAC. The magnitude of this effect varied, and was most marked in the frontal cortex. These results suggest that, in order for DOPAC to be transported from the central nervous system via a probenecid-sensitive transport system, it must first be conjugated. Additionally, it appears that the rates of synthesis, metabolism, and transport for both free and conjugated DOPAC may vary greatly among different dopamine-containing brain regions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1977

Norepinephrine levels in experimental spinal cord trauma. Part 1: Biochemical study of hemorrhagic necrosis.

Levels of norepinephrine (NE) in the spinal cord tissue of nontraumatized cats are highest in the cervical and lumbar enlargements. A rather uniform but slightly increasing concentration gradient from cephalad to caudad is observed in the thoracic segments. A 500 gm-cm trauma at the T-5 or C-7 spinal cord segment did not demonstrate any significant increase in NE levels measured sequentially over a 4-hour period after trauma. Dopamine levels could not be detected in the nontraumatized or traumatized cat spinal cords. Four traumatized cats treated with alpha methyl tyrosine, a tyrosine hydroxylase inhibitor, and followed clinically for 5 months showed no improvement in neurological function when compared to untreated traumatized cats. This study does not support the norepinephrine hypothesis of experimental spinal cord trauma.

Animals↗
PubMed1977

Norepinephrine levels in experimental spinal cord trauma. Part 2: Histopathological study of hemorrhagic necrosis.

Alpha methyl tyrosine (AMT) or reserpine administered intravenously 24 hours before sacrificed in the nontraumatized cat resulted in significant reduction in tissue levels of norepinephrine (NE) tested at the T-5 spinal cord level. Phenoxybenzamine given 2 hours before sacrifice did not alter NE levels at T-5. Histological sections of spinal cord examined 1 hour after a 500-gm-cm trauma at the T-5 level in cats, pretreated 24 hours before trauma by a single dose of AMT or reserpine demonstrated no reduction of gray or white matter hemorrhages when compared tocontrols. In cats pretreated with phenoxybenzamine 2 hours before trauma there was a marked reduction of hemorrhages at 1 hour posttrauma when compared to controls. The animals treated with phenoxybenzamine had a 32% reduction of systemic blood pressure before trauma, demonstrated no pressor response to spinal cord trauma, and were severely hypotensive posttrauma. It is concluded that posttraumatic blood pressure has greater etiological significance in the pathogenesis of experimental spinal cord hemorrhages than tissue levels of NE.

Animals↗
PubMed1976

Dopaminergic neurons: an in vivo system for measuring drug interactions with presynaptic receptors.

An in vivo system has been used to investigate the ability of dopamine agonists and antagonists to alter dopamine synthesis by acting at what appear to be presynaptic dopamine receptors. In order to eliminate postsynaptically induced changes in dopamine synthesis caused by the effects of these drugs on the firing rate of dopamine neurons, gammabutyrolactone was administered to block impulse flow in the nigro-neostriatal pathway. The accumulation of Dopa in the rat striatum after administration of Dopa decarboxylase inhibitor was used as an index of striatal tyrosine hydroxylase activity. It was found that administration of the dopamine agonists, apomorphine or ET-495 [1-(2-pyrimidyl)-piperonyl-piperazine], modified the apparent activity of striatal tyrosine hydroxylase when impulse flow was blocked in dopamine neurons. This presynaptic effect of apomorphine could be prevented by low doses of loxapine haloperidol and spiroperidol. Chlorpromazine, fluphenazine, and thioridizine were much less effective than the butyrophenones in blocking the effects of apomorphine. Molindone and (+) butaclamol, but not (-) butaclamol, reversed the presynaptic agonist effects, pimozide was a weak blocker and clozapine had no effect at all. All these neuroleptics except (-) butaclamol caused a significant increase in Dopa accumulation when impulse flow was intact. Compared with haloperidol the phenothiazines and pimozide appeared less potent in reversing the presynaptic effects of apomorphine than in blocking the behavioral effects of this agonist. Possible functional significance of the presynaptic dopamine receptors are considered.

4-Butyrolactone↗
PubMed1976

Effect of anesthetic doses of gamma-hydroxybutyrate on the acetylcholine content of rat brain.

Gamma-hydroxybutyrate administered in anesthetic doses produces a time dependent increase in the levels of rat barin acetylcholine. A maximal increase in whole brain and subcortical levels of acetylcholine is observed about 15 min after administration of the lactone form of the drug. A similar GHB-induced increase in acetylcholine is observed in the striatum and a 75% increase in the hippocampus 15 min after administration of the drug. A good temporal correlation was not obtained between the increase in acetylcholine and the depth of anesthesia produced by the drug. Gamma-hydroxybutyrate did not cause a significant change in the striatal or hippocampal levels of choline. Possible mechanisms involved in the production of this increase in acetylcholine are discussed.

4-Butyrolactone↗
PubMed1976

Dopaminergic neurons: reversal of effects elicited by gamma-butyrolactone by stimulation of the nigro-neostriatal pathway.

In vivo studies demonstrate that administration of gamma-butyrolactone, a precursor of gamma-hydroxybutyric acid causes a rapid increase in endogenous levels of striatal dopamine and an increase in tyrosine hydroxylase activity measured by following the short term accumulation of dihydroxyphenylalanine. The increase in dopamine produced by GBL is blocked by stimulation of the nigro-neostriatal pathway. If dopamine is allowed to accumulate for 30 min following administration of GBL this increased dopamine can be released by stimulation of the nigro-neostriatal pathway. Maintenance of neuronal activity in the nigro-neostriatal pathway by continuous stimulation at a physiological frequency of 3/s effectively blocks the ability of GBL to cause an increase in tyrosine hydroxylase activity in the striatum on the stimulated side. Tyrosine hydroxylase activity in the non-stimulated contralateral striatum is increased over 100% by administration of GBL. Stimulation of the nigro-neostriatal pathway 30 min after GBL administration causes about a 500% increase in the accumulation of dihydroxyphenylacetic acid in the striatum on the stimulated side. These results suggest that the increased dopamine is present in a pool which is releasable by neuronal stimulation and is subsequently exposed to MAO. These results are also consistent with the hypothesis that GBL activates tyrosine hydroxylase and increases endogenous dopamine levels primarily by blocking impulse flow in central dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid.

Stimulation of the nigro-neostriatal or mesolimbic dopamine pathway results in a stimulus dependent increase in the accumulation of dihydroxyphenylacetic acid (DOPAC) in the neostriatum and olfactory tubercles, respectively. A block of impulse flow induced pharamacologically by administration of gamma-butyrolactone or by placement of a lesion in the dopamine pathway results in a decrease in the steady state levels of DOPAC. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce a predictable change in the brain levels of DOPAC. Drugs which increase impulse flow in nigro-neostriatal or mesolimbic dopamine neurons increase DOPAC levels in the striatum and olfactory tubercles and drugs which reduce impulse flow cause a reduction in DOPAC. Pargyline, a monoamine oxidase inhibitor, causes a rapid depletion of striatal DOPAC suggesting that this metabolite is rapidly cleared from the brain. Administration of benztropine, a potent inhibitor of dopamine reuptake, causes a significant decrease in striatal DOPAC and partially prevents the stimulus-induced increase in the accumulation of DOPAC. These observations together with the finding that about 85% of the DOPAC in the striatum disappears when the dopamine neurons in the nigro-neostriatal pathway are destroyed suggests that the majority of striatal DOPAC is formed within the dopaminergic neurons and may reflect the metabolism of dopamine which has been released and recaptured. We conclude that short-term changes in brain levels of DOPAC appear to provide a useful index of alterations in the functional activity of central dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗