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Biomedical subjects

G Curzon

Publications and source records attributed to G Curzon.

At least 109 records · Page 6Linked to original sources
PubMed1983

Roles of dopamine and 5-hydroxytryptamine in stereotyped and non-stereotyped behaviour.

The roles of dopamine (DA) and 5-hydroxytryptamine (5-HT) in stereotyped and non-stereotyped components of the classical behavioural syndromes induced by 5-HT and DA were investigated by studying (a) behavioural interactions between the DA agonist apomorphine and the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and (b) the effects of depletion of 5-HT on the behavioural responses to amphetamine and p-chloroamphetamine. In agreement with evidence [Andrews, Fernando and Curzon (1982) Neuropharmacology 21:63-68] that non-stereotyped (i.e. body shakes and hind limb abduction) and stereotyped (i.e. head weaving and reciprocal forepaw treading) behaviour induced by d-amphetamine (25 mg/kg, i.p.) were inhibited and enhanced respectively by DA, apomorphine inhibited two non-stereotyped behavioural responses induced by 5-MeODMT (hind limb abduction and Straub tail) but enhanced reciprocal forepaw treading. However, head weaving was inhibited. Evidence indicated that behaviour induced by DA (whether stereotyped or not) was inhibited by 5-HT. Thus, the induction by apomorphine of sniffing and mouth movements was enhanced when the synthesis of 5-HT was inhibited. Also, p-chloroamphetamine caused sniffing and mouth movements only when 5-HT synthesis was inhibited. Under the latter conditions, while most classical behavioural responses associated with 5-HT did not occur, hind limb abduction persisted. Similarly, amphetamine (25 mg/kg) caused hind limb abduction and forepaw treading even when 5-HT was almost completely depleted. These results may indicate that the amine releasers have some direct 5-HT agonist properties. Results in general indicate the multiplicity of behavioural interactions between DA and 5-HT.

Animals↗
PubMed1983

Determination of brain 5-hydroxytryptamine turnover in freely moving rats using repeated sampling of cerebrovascular fluid.

A simple technique is described for repeated sampling of cerebrospinal fluid (CSF) from the freely moving rat and its use in the determinations of 5-hydroxytryptamine (5-HT) turnover validated. A catheter, constructed from polyethylene tubing (PP10) was implanted via a cranial approach into the cisterna magna and x-ray studies confirmed that the catheter avoided the cerebellum. 5-HT turnover was determined from the rate of rise of 5-hydroxyindoleacetic acid (5-HIAA) in both CSF and brain following an injection of probenecid (200 mg/kg i.p.). Concentrations of 5-HIAA, 5-HT and tryptophan were determined by high pressure liquid chromatography. Turnover values for individual rats were obtained using CSF samples. After p-chlorophenylalanine treatment (when brain 5-HT was depleted by 43%) 5-HT turnover values obtained were comparably reduced whether determined from CSF (-67%) or brain (-74%). Thus differences of rat brain 5-HT turnover are proportionately reflected by CSF measurements. The method for sampling of CSF should be applicable in a wide range of pharmacological and physiological situations.

Animals↗
PubMed1982

Enhancement of footshock-induced analgesia by spinal 5,7-dihydroxytryptamine lesions.

The analgesia induced by 30-s footshock (1 mA) is enhanced and attenuated by decreasing and increasing the extraneuronal availability of serotonin (5-HT), respectively. In the present work we have shown the effect to be mediated by spinal 5-HT systems as the response was increased by depletion of spinal but not brain 5-HT following injection of 5,7-dihydroxytryptamine into the spinal cord or raphe magnus. Injection of 5,7-DHT into the medial raphe which depleted brain but not spinal 5-HT was without effect.

5,7-Dihydroxytryptamine↗
PubMed1982

Analgesia induced by brief footshock is inhibited by 5-hydroxytryptamine but unaffected by antagonists of 5-hydroxytryptamine or by naloxone.

Exposure to footshock (1 mA) for 30 sec induced a marked analgesia that was enhanced by pretreatment with the 5HT synthesis inhibitor, p-chlorophenylalanine, and attenuated by the 5HT releasing drugs p-chloroamphetamine and fenfluramine, by the 5HT re-uptake inhibitor, fluoxetine and by the 5HT agonists, 5-methoxy-N,N-dimethyltryptamine and MK212. However, agonists, quipazine and trifluoromethylphenylpiperazine, with greater reported affinities for 5HT binding sites on rat brain membranes than MK212 were without effect as were the antagonists metergoline, methysergide, cyproheptadine, mianserine and methiothepin. The specific opioid antagonist naloxone was also without effect. The results in general indicate that analgesia induced by brief footshock (1 mA, 30 sec) is inversely related to 5HT availability but there is little evidence of involvement of known 5HT receptors.

Analgesia↗
PubMed1982

Differential involvement of dopamine-containing tracts in 5-hydroxytryptamine-dependent behaviours caused by amphetamine in large doses.

Dopamine (DA) concentrations in the rat striatum and/or nucleus accumbens were decreased by lesions in the nigra, ventral tegmentum, striatum and accumbens induced by 6-hydroxydopamine. These affected a range of DA- and 5-hydroxytryptamine-(5HT) dependent behaviours induced by 25 mg/kg of D-amphetamine as follows. Changes in DA-dependent behaviour (forward locomotion, head bobbing) occurred which were consistent with DA terminals in the accumbens and striatum being required for locomotor and stereotypical behaviour, respectively. A repetitive 5HT-dependent behaviour (head weaving) was decreased by lesions which depleted striatal DA. A 5HT-dependent behaviour with repetitive and locomotor elements (reciprocal forepaw treading) was only decreased by the nigral and tegmental lesions which depleted DA in both the striatum and the accumbens (and presumably also in other regions). These results suggest that 5HT-dependent behaviours of stereotypical character also require DA. Conversely, two 5HT-dependent behaviours, without obvious stereotypical or locomotor elements (body shakes, hind limb abduction), were not decreased by any of the lesions (and increased by some). Backward walking was markedly inhibited by lesions which decreased striatal DA. The above evidence for different relationships between each of the 5HT-dependent behaviours studied and DA-containing systems implies that these behaviours are separately mediated. It may clarify previous disagreement on the role of DA in these behaviours.

Animals↗
PubMed1982

Brain transmitter precursors and metabolites in diabetic ketoacidosis.

Patients studied during recovery from an episode of ketoacidotic diabetes had raised blood glucose, plasma free fatty acid and plasma free tryptophan concentrations. Plasma total tryptophan was decreased. Well controlled diabetics showed normal values. The ketoacidotic patients had increased lumbar CSF tryptophan and 5-hydroxyindoleacetic acid concentrations. Plasma tyrosine and CSF tyrosine and homovanillic acid concentrations were normal in both diabetic groups. The results are discussed in relation to somewhat similar findings in uraemic and hepatic encephalopathy and to changes in rats with streptozotocin diabetes.

Adult↗
PubMed1981

Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity.

Studies are described on the effect of plasma tryptophan changes on brain 5HT synthesis in man and rat. Results show that human brain 5HT synthesis is influenced by the supply of tryptophan to the brain. This is indicated by: (a) significant correlations between plasma free tryptophan and CSF 5HIAA concentrations; (b) raised cortical 5HT concentrations after infusing tryptophan. In rat experiments, determinations of brain tryptophan uptake from a bolus of plasma injected into the carotid artery showed: (a) increased uptake when bolus free tryptophan was raised and total tryptophan kept constant; (b) unchanged uptake when bolus free tryptophan was kept constant and total tryptophan decreased. Brain tryptophan uptake from a buffer bolus was decreased by large neutral amino acids. Plasma total tryptophan could be rapidly decreased and free tryptophan increased by briefly disturbing food deprived rats. When free tryptophan concentration rose markedly there was an associated increase of brain tryptophan and 5HT turnover. Studies of shock provoked analgesia in rats and cortical evoked potentials in man both suggest that physiological variations of serotonergic activity are sufficient to influence these measures. This raises the possibility that moderate changes of tryptophan supply to the brain could, in some circumstances, alter serotonergic activity.

Amino Acids↗
PubMed1981

Brain 5-hydroxytryptamine metabolism after portocaval anastomosis: relationship with ambulation.

Chronic portocaval anastomosis (PCA) increased tryptophan and 5-hydroxyindoles in rat brain regions. PCA rats ambulated less than sham operated animals but showed positive correlations between ambulation and indices of brain 5-hydroxytryptamine (5-HT) metabolism, i.e., plasma free tryptophan, plasma non-esterified fatty acid, tryptophan in all brain regions, and 5-HT or 5-hydroxyindoleacetic acid in some regions. Results suggest a positive and non-causal association between motor activity and 5-HT metabolism in the PCA rats reflecting parallel responses of both variables to environmental stimulation. This may be superimposed on a normal inverse and causal relationship between motor activity and 5-HT metabolism.

Animals↗
PubMed1981

Indolic substances in plasma, cerebrospinal fluid, and frontal cortex of human subjects infused with saline or tryptophan.

Psychiatric patients undergoing the psychosurgical operation of stereotactic subcaudate tractotomy were infused intravenously with either saline or L-tryptophan (15 mg/kg/h). Plasma, lumbar cerebrospinal fluid (CSF), ventricular CSF and a specimen of frontal cortex were collected. The relationships of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentration of tryptophan in the cortex and CSF were investigated. Tryptophan infusion resulted in plasma tryptophan values comparable to those found after oral doses used in treating depression or insomnia, and about sixfold increases of tryptophan in the cerebral cortex. Increased brain 5-hydroxytryptamine synthesis was indicated by significant rises of CSF 5-hydroxyindoleacetic acid. The concentration of plasma free tryptophan was a better predictor than plasma total tryptophan of cortex tryptophan concentration. As all correlation coefficients of plasma versus brain or plasma versus ventricular CSF tryptophan concentrations were decreased when allowance was made for differences of concentration of large neutral amino acids, the results suggest that the role of these substances within their physiological range as inhibitors of tryptophan transport to the brain may previously have been overemphasised.

Cerebral Cortex↗
PubMed1981

Effects of long-term low dietary tryptophan intake on determinants of 5-hydroxytryptamine metabolism in the brains of young rats.

The relationship between plasma and brain tryptophan (TRP) concentrations and brain 5-hydroxytryptamine (5-HT) metabolism was studied in weanling rats fed diets containing either 0.4 g or 1.45 g TRP/100 g casein hydrolysate. Both groups gained weight comparably though food intakes were generally higher in the low-TRP group. Severe depletion of plasma total and free TRP and of brain TRP, 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) occurred within 1 day of feeding the 0.4% TRP diet. Levels became stable after 7 days. The decreased brain TRP concentration of the rats on the 0.4% TRP diet did not cause a compensatory rise of the tryptophan hydroxylase (TRP OHase) activity in vitro. In the low-TRP group, neither plasma free TRP nor total TRP correlated significantly with brain TRP and although plasma TRP/large neutral amino acid (NAA) ratios (TRP/NAA) correlated significantly (P less than 0.05) with the time course of brain TRP, this statistical relationship depended almost completely on the variation of the TRP values alone. In the higher TRP group none of these correlations were significant. A plot of mean plasma free TRP versus brain TRP gave two distinct regression lines with similar slopes and corresponding to values before and after 7 days on the diet. The time course of brain 5-hydroxyindole concentrations did not parallel those of brain TRP and suggested that changes of TRP OHase activity also had an influence on 5-HT synthesis.

Aging↗
PubMed1981

A comparison of an improved o-phthalaldehyde fluorometric method and high pressure liquid chromatography in the determination of brain 5-hydroxyindoles of rats treated with L-tryptophan and p-chlorophenyl-alanine.

1 The determination of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) by reaction with o-phthalaldehyde (OPT) in the presence of cysteine and subsequent fluorometry was compared with determination by a new high pressure liquid chromatography (h.p.l.c.) electrochemical method. 2 The methods were used to investigate a claim that the OPT method gives falsely high brain 5-HT values for rats given tryptophan (greater than 25 mg/kg i.p.) and as a consequence an inhibition of 5-HT synthesis by tryptophan is obscured. 3 High concentrations of tryptophan caused some increase of fluorescence when added to 5-HT solutions and carried through the OPT method, e.g. tryptophan (80 micrograms/ml) gave fluorescence identical to 5-HT (0.13 micrograms/ml). This interference was decreased by more than half and the sensitivity of the method increased if cysteine was added at more stages and fluorescence developed at 77 degrees C instead of 100 degrees C. 4 The h.p.l.c. and modified OPT methods did not give significantly different mean brain 5-HT or 5-HIAA values in rats given 0,25,100,250 mg/kg L-tryptophan though values were somewhat higher by the OPT method with the highest dose. This method gave significantly higher residual brain 5-HT values (12% of control) than did the h.p.l.c. method (8% of control) after inhibiting 5-HT synthesis by p-chlorophenylalanine (150 mg/kg X 3). 5 There was no indication that tryptophan inhibited 5-HT synthesis even when brain tryptophan was increased about 30 fold (from 3.8 to 124 micrograms/g). 6 Results confirm the general reliability of the OPT method although h.p.l.c. has some advantages i.e. separation of 5-hydroxyindoles from tryptophan, greater sensitivity, ease of automation.

Animals↗