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D D Godse

Publications and source records attributed to D D Godse.

18 recordsLinked to original sources
PubMed1986

Further characterization of brain 3,4-dihydroxyphenylethyleneglycol (DHPG) formation: dependence on noradrenergic activity and site of formation.

The dependence of brain and plasma 3,4-dihydroxyphenylethyleneglycol (DHPG) formation upon CNS noradrenergic neutronal activity was evaluated following manipulations that are known to alter the firing rate of the locus coeruleus (LC) neurons and as a consequence, noradrenaline (NA) release and turnover. In addition, the relative degree of intraneuronal formation of brain DHPG was assessed by studying the metabolism of released NA during uptake inhibition. Electrical stimulation of the LC for 20 min induced an increase in rat cortical (40-42%), hypothalamic (22-29%) and plasma (68-79%) total DHPG and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels. Two hours following administration of the alpha-2 adrenoceptor antagonist yohimbine (10 mg/kg, i.p.), rat brain cortical conjugated DHPG and MHPG as well as free MHPG concentrations were increased whereas cortical free DHPG levels remained unchanged. The same treatment also increased plasma total DHPG and MHPG levels. In mice given the NA uptake inhibitor desipramine (10 mg/kg, i.p.) 2 h prior to sacrifice, brain free DHPG and MHPG concentrations were significantly reduced by 30 and 40%, respectively, whereas yohimbine (1-20 mg/kg, i.p.) induced a dose-dependent increase in brain DHPG (60-80%) and MHPG (60-220%) concentrations. Pretreatment with desipramine (10 mg/kg, i.p.) 30 min prior to yohimbine reduced, in rat, or abolished, in mice, the yohimbine-induced elevation of brain DHPG levels. In contrast, desipramine augmented the effect of yohimbine on brain MHPG levels resulting in a shift to the left of the dose response curves. These findings indicate that brain and plasma DHPG levels are sensitive to changes in brain noradrenergic neuronal impulse flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Elevated 3,4-dihydroxyphenylethyleneglycol (DHPG) excretion in dexamethasone resistant depressed patients.

Urinary and plasma DHPG and MHPG were estimated in patients with MADD and showing DST non-suppression as compared to those with normal suppression. Day and night 12h urine collections and morning plasma samples were analyzed by GC-MS for total MHPG and DHPG and free MHPG levels. Urinary DHPG excretion was significantly elevated in DST non-suppressors compared to suppressors, but no differences were found in urinary MHPG or plasma glycol levels. Elevated DHPG excretion in DST non-suppressors suggests that increased peripheral sympathetic NE activity occurs in association with dexamethasone resistance in MADD.

Adult↗
PubMed1985

Studies on the utility of urinary 3,4-dihydroxyphenylethylene-glycol (DHPG) measurement.

The utility of urinary DHPG measurement as an index of NE function was evaluated in an animal model by determining its excretion following pharmacological manipulations that are known to alter noradrenergic activity. Acute desipramine (DMI) administration (10 mg/kg, i.p., b.i.d.) significantly reduced urinary DHPG (-26%) but not MHPG (-18%) excretion. Acute yohimbine administration (5 mg/kg, i.p., b.i.d.) significantly increased urinary DHPG and MHPG levels to a similar extent (+46%). These findings suggest that urinary DHPG levels also provide a sensitive indicator reflecting changes in NE neuronal activity. Further, DHPG may be a better measure of NE metabolism than MHPG to assess the efficiency of the NE neuronal uptake system.

Animals↗
PubMed1979

Bufotenine esters.

Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl esters of bufotenine were prepared for future pharmacological evaluation. Unexpectedly, it was found that these esters all possess a relatively high affinity for the serotonin receptors of the isolated rat stomach fundus preparation. A semiquantitative chromatographic measurement of ester hydrolysis suggests that extensive hydrolysis of the esters to bufotenine does not occur under the conditions of the affinity assay.

Animals↗
PubMed1978

5-Hydroxytryptophol in human cerebrospinal fluid: quantitative determination by gas chromatography-mass spectrometry using a deuterated internal standard.

Procedures for the quantification of 5-hydroxyindole-3-ethanol, or 5-hydroxy-tryptophol (5-HTOL), in human cerebrospinal fluid are described. 5-HTOL was determined as its di-pentafluorpropionyl derivative. Deuterium labelled 5-hydroxyindole-3-ethanol-a,a,b,b-d4 (5-HTOL-d4) was used as internal standard. Mass fragmentography was performed by double ion monitoring each for 5-HTOL and 5-HTOL-d4 and their ratios were determined for specificity. Assay sensitivities of 0.15 ng/ml were achieved using 2.0 ml of cerebrospinal fluid. Free 5-HTOL concentrations in human cerebrospinal fluid were determined to be 0.73 +/- 0.44 ng/ml (mean +/- S.D.) (range 0.33-2.11 ng/ml) from 15 patients with various neurological disorders, and 0.85 +/- 0.30 ng/ml (range 0.48-1.32 ng/ml) from 9 subjects who complained of low back pain but did not show signs of neurological illnesses.

Chromatography, Gas↗
PubMed1978

Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice.

Two experiments examined the possibility that mice rendered obese by systemic injection of goldthioglucose (GTG) possess altered endogenous levels of brain norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine or 5HT) and/or 5-hydroxyindoleacetic acid (5HIAA). In the first experiment, single-housed GTG-obese mice were found to have normal brain DA and 5HIAA but 14% less NE and 6% less 5HT than controls. This neurochemical profile was strikingly similar to that previously reported for rats rendered obese by ventromedial hypothalamic lesions (i.e., normal DA and 5HIAA, 19% less NE, 7% less 5HT). However, in the second experiment, equally obese GTG mice pair-housed with non-obese controls showed normal DA, 5HIAA, and NE but 9% more 5HT than controls. In other words, absolute levels of these brain substances were inconsistent with respect to obesity across experiments. On the other hand, when ratios of all possible combinations of these compounds were compared across experiments, only 5HT/NE ratios were consistently different (higher) in GTG mice. In addition, reliable inverse correlations were obtained between weight gain parameters and brain 5HT/NE or 5HIAA/NE ratios for GTG mice. These findings suggest that interactions between brain 5HT and NE neurons may contribute to the overeating and obesity which occur in mice after GTG administration.

Animals↗
PubMed1977

A gas chromatographic-mass spectrometric (GC-MS) assay for 3-methoxy-4-hydroxyphenethyleneglycol and vanilmandelic acid in human serum.

Procedure for the quantification of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and vanilmandelic acid (VMA) in human serum are described. MHPG was selectively acetylated then determined as its 4-acetyl-di-trifluoroacetyl derivative and VMA as its di-pentabluoropropionyl-methyl ester. Deuterium-labeled MHPG and VMA were used as internal standards. Each of these metabolities and the resprective internal standards was recorded by double ion monitoring respectively, and the ratios were determined for specificity. Assay sensitivities of 1.0 ng/ml for MHPG and 2.0 ng/ml for VMA were achieved using 0.5 ml of serum. Total and free MHPG concentrations in human serum were determined to be 16.5 ng/ml +/- 4.4 (S.D.) and 4.6 ng/ml +/- 1.0 respectively from 10 normal male subjects. Free VMA concentrations were 7.0 ng/ml +/- 1.5; thus the ratio of MHPG/VMA was calculated to be 2.4 +/- 0.7 in these subjects. Of these two major normal metabolites of norepinephrine, MHPG is regarded to be largely derived from the central nervous system while VMA is from the periphery. The procedures are highly specific as well as simple and sensitive enough to permit simultaneous measurement of these two metabolites in a series of multiple samples from an individual.

Adult↗
PubMed1977

CNS monoamine metabolism in bipolar affective disorder. Evaluation using a peripheral decarboxylase inhibitor.

Carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, inhibits the peripheral synthesis of nor-adrenaline, serotonin, and tryptamine. By reducing the peripheral component of end-products of these amines in urine, a more accurate assessment of central nervous system (CNS) amine metabolism is provided. Urinary 5-hydroxyindoleacetic acid (5-HIAA), tryptamine, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured over ten days in ten normal controls and eight bipolar depressives. After a three-day baseline period, carbidopa, 100 mg three times a day, was given for seven days. While the patients tended to excrete less MHPG in the baseline period, these differences became somewhat larger, and statistically significant when peripheral contributions were reduced with carbidopa. While carbidopa resulted in striking inhibition of tryptamine excretion, and smaller decreases in the excretion of 5-HIAA and MHPG, evidently from storage pools, there were no significant differences in degree of inhibition between patients and controls. Absolute values of 5-HIAA and tryptamine were similar for both groups, during the baseline and again with carbidopa. These results after carbidopa are compatible with a central catecholaminergic deficit in bipolar depressives and the use of urinary MHPG as an index of CNS catecholamine function.

Adolescent↗
PubMed1977

The effect of a peripheral decarboxylase inhibitor (carbidopa) on monoamine and neuroendocrine function in man.

Carbidopa, a selective extracerebral decarboxylase inhibitor, was given to 10 normal volunteers to determine its effects on endogenous catecholamine, indoleamine, and endocrine function. Tryptamine, which is largely extracerebral in origin, was inhibited markedly (80 percent) by the carbidopa; 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenolglycol (MHPG) excretion also were inhibited by the drug but not to the same degree as tryptamine. These differential results may be due partly to the higher central nervous system origin of the 5-HIAA and MHPG but also to a peripheral "stores" effect. In addition, carbidopa resulted in significant increases in plasma prolactin and a small but significant decrease in plasma glucagon.

Adult↗
PubMed1976

Urinary cyclic AMP in relation to lithium treatment in manic-depressive illness.

Urnary cyclic AMP was measured longitudinally in six patients with bipolar affective disorder. The values varied from 3.55 to 19.0 mugmol/24 hours with considerable variation between subjects. Three of these patients improved with administration of lithium carbonate. This improvement was not correlated with a change in cyclic AMP excretion. Five normal male volunteers were studied over a 5-day period. The urinary excretion for this group showed the same large intersubject variability but smaller intrasubject variation as was found for the patient group. It is suggested that erroneous results may be obtained for urinary cyclic AMP excretion if mean group values are used from patients not studied longitudinally.

Adult↗
PubMedDate not supplied

Taming effects of handling on 6-hydroxydopamine induced ratge.

The purpose of this experiment was to determine the importance of handling to the expression of hyperemotional behaviors, i.e., rage, known to occur after chronic depletion of brain norepinephrine (NE) and dopamine (DA) following central injection of 6-hydroxydopamine (6-OHDA) in rats. Five min of handling per day for 6 consecutive days reduced resistane to capture as well as the magnitude and frequency of startle responding following one 300 mug injection of 6-OHDA intracisternally. Both 6-OHDA-handled and 6-OHDA-unhandled rats showed comparable levels of brain NE, DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), comparable resting levels of plasma corticosterone, and comparable adrenal weights. These data demonstrate the importance of handling to the expression of 6-OHDA-induced rage and emphasize the importance of controlling for handling as a variable which can significantly affect the assessment of rage by behavioral criteria in this animal model of hyperemotionality.

Anger↗
PubMedDate not supplied

Determination of picogram levels of brain serotonin by a simplified liquid chromatographic electrochemical detection assay.

A simplified assay is described for measurement of picogram amounts of serotonin (5-HT) by high pressure liquid chromatography with electrochemical detection (LCEC). The procedure involves pre-purification of brain 5-HT by adsorption on Amberlite CG-50. Serotonin is subsequently resolved and detected by LCEC on Zipax SCX resin. The present method gives working sensitivities of at least 100 pg, tissue recoveries of 95% and very low interassay variability (coefficient of variation = 3%). Determination of rat brain area 5-HT by this LCEC method is described and compared to other high sensitivity methods.

Animals↗