Origin and distribution of 3-methoxy-4-hydroxyphenylglycol in body fluids.
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Biomedical subjects
Publications and source records attributed to A E Halaris.
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Microinjections of the excitatory neurotoxin kainic acid into the lateral hypothalamus of rats produced a period aphagia and adipsia. Kainate-treated rats displayed transient motor effects during the first hours after the injection but did not show the persisting sensory-motor and arousal disturbances typically observed in animals with electrolytic lesions in this part of the hypothalamus. Histological examination revealed a significant reduction in the number of nerve cell bodies in the lateral hypothalamus. Silver-stained material indicated no evidence of damage to fiber systems passing through the affected region. Assays of dopamine in hypothalamus, striatum, and telencephalon did not indicate significant differences between experimental and control animals. These results are in agreement with recent reports of the anatomical and biochemical effects of intracerebral kainic acid injections and suggest that the observed effect on feeding behavior is related to the destruction of neurons in the lateral hypothalamus.
Improved methods are described for the fluorimetric determination of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan (TRP) in plasma, platelet and RBC blood compartments. The methods for 5-HT and 5-HIAA utilize ion exchange chromatography and allow simultaneous determinations to be made on the same blood sample. The tryptophan assay is a modification of an existing extraction method. All of the 5-HT in whole blood was found to be associated with the platelet fraction (122.6 ng/ml), whereas all 5-HIAA was distributed between the plasma (78.3 ng/ml) and RBC (124.0 ng/ml) compartments. Tryptophan was found in all three compartments although the majority of this amino acid was in the plasma (4.3 microgram/ml) and RBC (1.7 microgram/ml) fractions.
The ascending projections of serotonin neurons of the midbrain raphe were analyzed in the rat using the autoradiographic tracing method. Axons of raphe serotonin neurons ascend in the ventral tegmental area and enter the medial forebrain bundle. A number of fibers leave the major group to ascend along the fasciculus retroflexus. Some fibers enter the habenula but the majority turn rostrally in the internal medullary lamina of the thalamus to innervate dorsal thalamus. Two additional large projections leave the medial forebrain bundle in the hypothalamus; the ansa peduncularis-ventral amygdaloid bundle system turns laterally through the internal capsule into the striatal complex, amygdala and the external capsule to reach lateral and posterior cortex, and another system of fibers turns medially to innervate medial hypothalamus and median eminence and form a contrelateral projection via the supraoptic commissures. Rostrally the major group in the medial forebrain bundle divides into several components: fibers entering the stria medullaris to terminate in thalamus; fibers entering the stria terminalis to terminate in the amygdala; fibers traversing the fornix to the hippocampus; fibers running through septum to enter the cingulum and terminate in dorsal and medial cortex and in hippocampus; fibers entering the external capsule to innervate rostral and lateral cortex; and fibers continuing forward in the medial olfactory stria to terminate in the anterior olfactory nucleus and olfactory bulb.
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An improved method is described for determining picogram quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma of humans and of other species. The method makes use of gas-liquid chromatography and electron capture detection. Low level nonlinearity of detector response was corrected by operating the detector in the pulsed rather then the customary steady state mode. Detector overloading was prevented by heat coagulation of plasma proteins and subsequent ultrafiltration. Sensitivity was significantly enhanced by utilizing a derivatizing agent carrying a higher number of electrophores. Baseline conditions are described and control values for plasma MHPG of human volunteers, Rhesus monkeys and rats are presented.
Axonal transport of protein and metabolites of L-[3H(G)]3, 4-dihydroxyphenylalanine ([3H]DOPA) was studied in the central noradrenaline neurons of the pontine nucleus locus coeruleus and was correlated with regional alterations of noradrenaline content following destruction of the nucleus. Unilateral lesions of the locus coeruleus produce a partial depletion of noradrenaline in the ipsilateral hypothalamus and telencephalon, indicating that these neurons project widely to the ipsilateral forebrain. Twenty-four to 48 h following local injections of 50 micronCi [3H]proline, locus coeruleus neurons take up labeled material and transport it, presumably as protein, to ipsilateral structures in the midbrain, diencephalon and telencephalon including the neocortex. Similarly 8 h after injection of 25 micronCi [3H]DOPA into the locus coeruleus, transport of material including catecholamines occurs to ipsilateral diencephalon and telencephalon. Axonal transport of proteins to telencephalic structures is greatly diminished by selective lesions of catecholamine terminals with 6-hydroxydopamine (6-OHDA) and following destruction of the medial forebrain bundle. These results provide further support for the view that noradrenaline neurons of the locus coeruleus nucleus project widely within the neuraxis to ipsilateral structures of the brain stem, diencephalon and telencephalon, including all cortical areas. In addition, evidence is presented for a contralateral projection with a similar distribution. The rate of axonal transport of labeled protein and metabolites of [3H]DOPA including [3H]catecholamines in central noradrenaline neurons is estimated to be 3-4 mm/h and is accordingly similar to that reported for noradrenaline neurons of the peripheral sympathetic nervous system.
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The purpose of the present study was to investigate the effects of complete lesions of the noradrenaline locus coeruleus neurons upon wakefulness and paradoxical sleep. Radiofrequency lesions of the nucleus were performed in 8 chronically implanted cats which were continuously recorded with an EEG for 5 days prior to and 21 days following the lesions, when they were sacrificed. In 3 of these animals amphetamine (2 mg/kg) was administered on one control day and on the 10th day post-lesion. Following sacrifice, monoamine content was assayed in discrete brain regions, and the lesion was examined in Nissl-stained sections of the pons. (1) The majority (x 69%) of the locus coeruleus was bilaterally destroyed by the lesions which only minimally exceeded the boundaries of the nucleus within the dorsolateral pontine tegmentum. Noradrenaline was depleted by a mean of 85% in the paleo- and neocortex and by a mean of 60% in the thalamus and midbrain. (2) EEG activation reappeared within 12-48 h following the lesion and represented a normal percentage of recording time on the 3rd and subsequent days post-lesion. The behavioral arousal and long-lasting EEG activation produced by amphetamine was qualitatively and quantitatively the same pre- and post-lesion. (3) Despite alteration of certain components, paradoxical sleep reappeared within 48 h and recovered to normal amounts by the second week post-lesion. Muscle atonia was permanently absent in 7 animals. Ponto-geniculo-occipital (PGO) spiking was acutely redistributed across all states and chronically reduced in frequency (by a mean of 50%) within paradoxical sleep. These results indicate that the noradrenaline locus coeruleus neurons are not necessary for the tonic maintenance of EEG activation that occurs in normal wakefulness and in amphetamine-produced arousal. Furthermore, these neurons are not necessary for the occurrence of paradoxical sleep, although they may be involved in modulation of PGO spiking.
A retractable wire knife was used to transect medial or lateral components of the MFB or its lateral projections to the striatum and amygdaloid complex. All cuts produced significant depletions of NE, DA, and 5-HT from telencephalon and striatum but little or no effect on hypothalamic NE or 5-HT. Two of our cuts resulted in aphagia and adipsia, the third in hyperphagia and obesity. A detailed correlational analysis of the magnitude and direction of the behavioral and biochemical consequences of our cuts indicated that the ingestive behavior of all of our experimental animals (including animals which had been aphagic and adipsic after surgery as well as animals which were hyperphagic and obese) was positively correlated with the concentration of DA in striatum and telencephalon and negatively correlated with telencephalic 5-HT. Less consistent evidence for facilitatory noradrenergic influences on food intake was also obtained. Our results suggest that the regulation of food intake may be the result of an interaction between telencephalic serotonergic mechanisms and dopaminergic pathways which exert opposite effects on ingestive behavior.
Aphagia and adipsia of equivalent duration were produced by knife cuts along the lateral border of the hypothalamus (PH cuts), or the medial surface of the globus pallidus (MP cuts) in male albino rats. Striatal dopamine (DA) was reduced by 75% in animals with PH cuts but only 50% by MP cuts. Hypothalamic norepinephrine was reduced 25% by PH cuts and was unaffected by MP cuts. Aphagia and adipsia were positively correlated with DA depletions only in rats with PH cuts. Presurgical catecholamine depletions produced by chronic injections of alpha-methyl-p-tyrosine did not alter the duration of aphagia or adipsia resulting from these knife cuts. However, following recovery of ingestive behavior, rats with PH and MP cuts were supersensitive to the anorexic effects of the dopamine-beta-hydroxylase inhibitor, diethyldithiocarbamate. Exaggerated anorexia was also observed after DA blockade by haloperidol or alpha-adrenergic blockade by phenoxybenzamine. The most pronounced effects of catecholamine blockade were observed in rats with PH cuts.
The concentration of NE, DA and 5-HT in forebrain, striatum, and hypothalamus was measured after zona incerta (ZI) lesions that have been shown to result in general hypodipsia; adipsia during periods of food deprivation; impaired or abolished drinking in response to osmotic challenges (but not polyethylene glycol); impaired drinking after systemic isoproterenol or central angiotensin; and impaired or abolished feeding in response to 2-deoxy-D-glucose. The lesions produced a significant (40-50%) depletion of forebrain NE but a correlational analysis of the behavioral and biochemical effects of the lesions failed to indicate a causal relationship. The lesions did not reliably affect (a) forebrain DA or 5-HT; (b) striatal DA or 5-HT; (c) hypothalamic DA, NE or 5-HT. The results of these experiments indicate that significant impairments in ingestive behavior can be demonstrated in animals with diencephalic lesions that do not result in striatal (or forebrain) DA depletions. This confirms previous behavioral analyses showing that ZI lesions which interfere with ingestive behavior do not produce the debilitating sensory or motor dysfunctions typical of the rat with lateral hypothalamic lesions.