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Biomedical subjects

C A Marsden

Publications and source records attributed to C A Marsden.

At least 199 records · Page 11Linked to original sources
PubMed1982

Withdrawal from chronic treatment with metergoline, dl-propranolol and amitriptyline enhances serotonin receptor mediated behaviour in the rat.

Acute treatment of rats with metergoline (2 mg/kg), a serotonin antagonist, prevented the behavioural syndrome produced by the serotonin agonist 5-methoxy-N',N'-dimethyltryptamine (2.5 mg/kg, 5MEODMT). dl-Propranolol (15 mg/kg) and amitriptyline (15 mg/kg) also inhibited the behavioural syndrome. The 5MEODMT behavioural syndrome was attenuated when metergoline or amitriptyline were administered daily for 14 days and 5MEODMT administered 30 min after the injection on day 14. This attenuation was not seen with chronic dl-propranolol treatment. When 5MEODMT was administered 72 h after the last injection of metergoline, amitriptyline or dl-propranolol on day 14, the behavioural syndrome was enhanced. The results suggest that withdrawal from chronic treatment with serotonin antagonists results in functional supersensitivity of serotoninergic neurones.

Amitriptyline↗
PubMed1982

Co-existence of thyrotrophin releasing hormone and 5-hydroxytryptamine in the skin of Xenopus laevis.

1. The location, release and re-synthesis of thyrotrophin releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) in the skin of Xenopus laevis (the South African clawed toad) have been determined using both morphological and analytical procedures. 2. High levels of TRH and 5-HT are located specifically within the dermal granular glands of X. laevis and discharged from these glands following alpha-adrenergic stimulation. 4. The common occurrence and separate production of high levels of TRH and 5-HT in amphibian skin may provide a model for studying the mechanisms of biosynthesis, interaction and release of these substances in mammalian tissues such as ventral spinal cord, where TRH and 5-HT are found in the same neurones.

Animals↗
PubMed1982

Localization and release of 5-hydroxytryptamine thyrotrophin releasing hormone and substance P in rat ventral spinal cord.

1. The highest spinal cord levels of 5-hydroxytryptamine (5-HT) and thyrotrophin releasing hormone (TRH) were found in the ventral lumbar cord, in contrast to substance P which was found predominantly in the dorsal cord. 2. 5,6- and 5,7-dihydroxytryptamine, administered into the lateral ventricles reduced 5-HT in the dorsal and ventral spinal cord by up to 90%. 3. There was a parallel reduction in substance P and TRH in ventral spinal cord while methionine-enkephalin and somatostatin in ventral and dorsal cord increased. 4. Reserpine and tetrabenazine depleted 5-HT and partially depleted substance P and TRH in the ventral cord, but had no effect on either methionine-enkephalin or somatostatin. 5. The rates of loss and recovery, after reserpine and tetrabenazine, of 5-HT were different from those of the two peptides. 6. Endogenous 5-HT and TRH release from slices of lumbar cord was enhanced by high potassium. 7. p-Chloroamphetamine and fenfluramine increased 5-HT release but reduced or had no effect on TRH release. The effect of p-chloroamphetamine on TRH release was not dependent on either the presence of 5-HT or 5-HT receptor activity. 8. The results are discussed in terms of the possible co-existence, co-storage and release of 5-HT, substance P and TRH in descending bulbospinal neurones.

Animals↗
PubMed1982

The effects of monoamine neurotoxins on peptides in the rat spinal cord.

The coexistence of two neuronally-localised peptides, substance P and thyrotropin-releasing hormone (TRH), in descending serotoninergic nerve fibres to the spinal cord was investigated using immunocytochemical and biochemical methods. Substance P-like material in the spinal cord was shown to be identical to the undecapeptide substance P by the criteria of gel filtration, high performance liquid chromatography and behaviour in substance P specific radioimmunoassays. Immunocytochemical staining for 5-hydroxytryptamine, substance P, and TRH showed that all three substances had a similar distribution in nerve fibres and terminals in the ventral and lateral grey matter of the spinal cord. After treatment with the serotonin neurotoxin 5,7-dihydroxytryptamine, neuronal elements containing 5-hydroxytryptamine, substance P and TRH degenerated and disappeared from these parts of the spinal cord in parallel with one another. Biochemical measurements of 5-hydroxytryptamine, substance P and TRH in the spinal cord after treatment with 5,7-dihydroxytryptamine confirmed that these three substances were all depleted from the ventral horn and, in addition, showed that there was a small depletion of substance P from the dorsal horn. Two other neuropeptides, somatostatin and methionine-enkephalin were not depleted from the spinal cord by treatment with 5,7-dihydroxytryptamine nor was substance P in other parts of the brain. Substance P in the spinal cord was unaffected by 6-hydroxydopamine, a drug known to destroy catecholamine-containing neurones. These results are consistent with coexistence of substance P and TRH together with 5-hydroxytryptamine in the descending axons and terminals of bulbospinal neurones.

5,6-Dihydroxytryptamine↗
PubMed1982

Thyrotrophin-releasing hormone analogues increase dopamine release from slices of rat brain.

Rat brain slices were incubated with a high concentration of K+, thyrotrophin-releasing hormone (TRH), or one of two biologically stable TRH analogues (CG 3509 or RX 77368). Basal release of endogenous dopamine, measured by electrochemical detection, was increased by K+ (30 mM) from slices of hypothalamus, septum, nucleus accumbens, and striatum. CG 3509 (10-(5) -10-(3) M) increased the release of dopamine from slices of nucleus accumbens, septum, and hypothalamus in a dose-dependent fashion, whereas RX 77368 (10-(4) M) increased the release of dopamine from the septum only. Neither analogue increased the release of striatal dopamine. The results provide further evidence for specific regional interactions between TRH and dopamine in rat brain.

Animals↗
PubMed1982

Differential pulse voltammetry in the anaesthetized rat: identification of ascorbic acid, catechol and indoleamine oxidation peaks in the striatum and frontal cortex.

1 Differential pulse voltammetric scans recorded using graphite paste working electrodes implanted in the striatum and frontal cortex of anaesthetized rats exhibited up to three distinct oxidation peaks at potentials between -0.1 and +0.5 V. 2 The first peak at about +0.12 V was selectively increased by the micro-infusion of ascorbic acid (5 X 10(-6) M) close to the surface of the working electrode implanted in either the striatum or the frontal cortex. 3 The second peak at about +0.22 V was selectively increased by micro-infusing either dopamine or 3,4-dihydroxyphenylacetic acid, (5 X 10(-6) M). 4 The third peak at approximately + 0.35 V was selectively increased in a dose-related manner by the micro-infusion of either 5-hydroxytryptamine, (7.5 X 10(-6) M to 7.5 X 10(-5) M) or 5-hydroxyindole-3-acetic acid, (2.5 X 10(-5) M to 6 X 10(-4) M). 5 The results show that differential pulse voltammetry can be used to obtain qualitative and quantitative information about catechol and indoleamine neurones in vivo.

Anesthesia↗
PubMed1981

The effects of 5-hydroxytryptamine-depleting drugs on peptides in the ventral spinal cord.

The ventral spinal cord content of several neuronally localised peptides was measured after treatment with a number of drugs which deplete spinal cord monoamines. Reserpine and tetrabenazine, but not p-chlorophenylalanine caused a partial depletion of ventral spinal cord substance P (SP) and thyrotropin-releasing hormone (TRH). Two other peptides, methionine-enkephalin and somatostatin were not depleted by any of the drugs. The rates of loss and recovery of SP and TRH after reserpine and tetrabenazine were different from that of 5-hydroxytryptamine (5-HT), though in the ventral spinal cord these two peptides probably coexist with 5-HT in the terminals of bulbospinal neurones. The results are discussed in relation to the possible costorage of SP and TRH with 5-HT in the same vesicles in nerve terminals in the ventral spinal cord.

Animals↗
PubMed1981

Effects of chronic modification of dietary fat and carbohydrate in rats.

1. Rats were fed on diets enriched with starch, sucrose, corn oil or beef tallow for 3 weeks and the activities of various enzymes in the liver were measured. 2. The mitochondrial glycerol phosphate acyltransferase activity was lower in rats fed on the starch diet than on the two high-fat diets. 3. The non-microsomal (presumably peroxisomal) dihydroxyacetone phosphate acyltransferase activity was higher in rats fed on the starch diet and corn-oil diets than in those fed on the sucrose and beef-tallow diets. Urate oxidase activity was higher in rats fed on the starch diet than in the three other groups. There were no significant differences in the activity of acyl-CoA oxidase among the groups. 4. The activity of soluble phosphatidate phosphohydrolase was not significantly different among the dietary groups. There were increases of 3.3--4.3-fold in this activity in the dietary groups 6h after injection of corticotropin. The equivalent increases for the mitochondrial glycerol phosphate acyltransferase were 1.4--1.6 fold. 5. The corticosterone responses to the corticotropin injection were not significantly different between dietary groups. However, the corticosterone response of the rats fed on the two high-fat diets was prolonged when the rats were given an acute load of fructose [Brindley, Cooling, Glenny, Burditt & McKechnie (1981) Biochem. J. 200. 275--283]. 6. Rats fed on the high-fat diets had higher concentrations of circulating cholesterol than those fed on the starch and sucrose diets. Serum triacylglycerol concentrations were lower in the rats fed on the starch diet than in the three other groups. 7. The results are discussed in terms of the relationship between diet, hormonal balance and hepatic glycerolipid metabolism.

Adrenocorticotropic Hormone↗
PubMed1981

Circadian variation in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine and p-chloroamphetamine in the mouse.

Circadian fluctuations were measured in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine (5-MeODMT) and p-chloroamphetamine (PCA) in male BK. TO mice. The effects of depleting brain 5-hydroxytryptamine (5-HT) with p-chlorophenylalanine (PCPA) on the 5-MeODMT in the mouse were also studied. Changes in brain 5-HT and 5-hydroxyindoleacetic (5-HIAA) were concomitantly determined. PCPA (400 mg/kg IP twice on consecutive days) significantly increased the number of head twitches induced by 5-MeODMT (5 mg/kg IV) on days 3 and 5 after the initial injection of PCPA when 5-HT and 5-HIAA were also significantly reduced. On day 12, there was no significant difference in the number of head twitches between mice administered PCPA and those given saline, and 5-HT and 5-HIAA levels were nearly back to normal. PCPA, using the same dose schedule, significantly reduced the number of head twitches induced by PCA when PCA was administered 24 h after the second injection of PCPA (day 3. Mice maintained on a 12-h light-dark cycle showed a maximum response to the direct 5-HT receptor agonist 5-MeODMT (5 mg/kg IV) towards the end of the dark period, when the 5-HT level was at its lowest. p-Chloroamphetamine, which causes release of 5-HT from pre-synaptic neurones, produced a peak head twitch response in the middle of the light period when 5-HT and 5-HIAA levels were maximal, while the response towards the end of the dark period was significantly less than that at other times tested. It is concluded that 5-HT receptor response shows a circadian rhythm related to both pre-synaptic availability of 5-HT and post-synaptic receptor sensitivity.

Amphetamines↗
PubMed1981

Location and release of TRH and 5-HT from amphibian skin.

The occurrence and release of thyrotrophin-releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) from amphibian skin have been described by previous investigators. In the present study, the precise location and site of release of TRH and 5-HT from the skin of Rana pipiens and Xenopus laevis have been examined using a combination of procedures including immunohistochemistry, HPLC, and radioimmunoassay. The results indicate that TRH is located specifically within the dermal glands of these species, and that both TRH and 5-HT are discharged from these glands following adrenergic stimulation. The origin and functional significance of these substances in amphibian skin granular glands are discussed.

Animals↗
PubMed1981

Effect of L-tryptophan on mouse brain 5-hydroxytryptamine: comparison of values obtained using a fluorimetric assay and a liquid Chromatographic assay with electrochemical detection.

5-Hydroxytryptamine (5-HT) in mouse brain and spinal cord was assayed in the same samples using a fluorimetric assay and a high pressure liquid chromatographic (HPLC) assay with electrochemical detection. The HPLC assay was able to detect levels of 5-hydroxytryptamine as low as 0.2-0.5 pmol. With the column (Vydac cation exchange), solvent system (acetate/citrate buffer, 0.1 or 0.2 M, pH 4.8-5.2) extraction procedure and electrode potential (+0.55 V) used, the HPLC assay was specific for 5-HT. When the electrode potential was increased to +0.9 V tryptamine could also be detected, with a longer retention time than 5-hydroxytryptamine. The percent-age increase in mouse brain 5-hydroxytryptamine after pargyline (75 mg/kg) and pargyline L-tryptophan (100 mg/kg) was very similar whether measured by fluorimetry or HPLC, although the fluorimetric assay gave consistently higher absolute values (24-32%) in both control and drug-treated animals. L-Tryptophan (25, 50 and 100 mg/kg) also increased brain 5-hydroxytryptamine with similar percentage increases with either assay method. There was a significant correlation (P less than 0.001) between the values obtained with the two assay methods. The results confirm the use of HPLC with electrochemical detection as a sensitive and specific assay method for 5-hydroxytryptamine and indicate its potential use for the assay of tryptamine, and the importance of determining the electroactivity and retention characteristics of any drugs used.

Animals↗
PubMed1981

Behavioural effects of long term inhibition of 5-hydroxytryptamine receptors using metergoline.

1. Rats were treated with acute and chronic schedules of metergoline (2.5 mg/kg I.P. twice daily) and acutely with dl-propranolol (15 mg/kg), amitriptyline (12.5 mg/kg) and fluoxetine (2 mg/kg). 2. Metergoline given both acutely and chronically blocked the behavioural response to the 5-hydroxytryptamine receptor agonist 5-methoxy-N1, N1-dimethyltryptamine (5MeODMT) (2.5 mg/kg I.P.). The response to 5MeODMT) was also blocked by acute administration of dl-propranolol and amitriptyline, but not fluoxetine. 3. Rats given chronic treatment with metergoline and then withdrawn from drug treatment for 3 days showed an enhanced response to 5MeODMT. 4. Chronic metergoline treatment caused an increase in ambulatory movement following 5MeODMT administration. 5. Exploratory behaviour, when measured under dark conditions, was reduced by chronic metergoline treatment. 6. The results suggest that supersensitivity to 5-hydroxytryptamine agonists can be induced by chronic treatment with an antagonist. Furthermore, metergoline and 5-methoxy-N1, N1-dimethyltryptamine may not act on identical receptor populations.

Amitriptyline↗
PubMed1981

Electrochemical monitoring of 5-hydroxytryptamine release in vitro and related in vivo measurements of indoleamines.

1. Electrochemical techniques have been used to measure release of endogenous 5HT from brain regions in vitro and to record electrochemical changes induced by drugs acting on 5HT neurones in the anaesthetised and unanaesthetised rat in vivo. 2. 5HT release in vitro was observed in all regions studied. The highest level of basal release was observed in the nucleus accumbens/septal region and hypothalamus and the lowest in the striatum. 3. High potassium (55 mM) increased release of 5HT in all regions, where their basal release was observed. 5HT release was also increased by p-chloroamphetamine (1-10 microM). 4. In rats anaesthetised with pentobarbitone, three electrochemical peaks were observed in the striatum, nucleus accumbens and frontal cortex at + 0.12 V, +0.2 V and + 0.35 V using a micro-graphite paste electrode and differential pulse voltammetry. 5. The peak at + 0.12 V was increased by micro-infusion of ascorbic acid (5 X 10(-6) M) and that at + 0.35 V by micro-infusion of 5HT (5 X 10(-6) M) and 5-hydroxyindole acetic acid (5HIAA) (5 X 10(-6) M). 6. p-Chlorophenylalanine (2 X 150 mg/kg) caused the loss of the peak at + 0.35 V. Fenfluramine (10 mg/kg) also decreased the peak at + 0.35 V. 7. The results indicate the validity of the in vitro technique and demonstrate the future potential of the in vivo method, though further studies are needed to determine the precise chemical nature of the changes in oxidation following administration of drugs acting on 5HT neurones.

Action Potentials↗
PubMed1979

Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry.

The possibility of using in vivo voltammetry to monitor 5-hydroxytryptamine (5-HT) release from brain tissue in freely moving unanaesthetized rats has been examined. A potential (+0.2 to +1.0 V) was applied to a micrographite electrode stereotaxically placed within a specific brain region and current changes following the oxidation of electroactive compounds in the vicinity of the electrode tip were recorded. Administration of p-chloroamphetamine (5 mg/kg) produced a large increase in current in the striatum and this could be prevented by pretreatment with p-chlorophenylalanine (150 mg/kg X 2) to deplete brain 5-HT or Fluoxetine (10 mg/kg) which prevents the uptake of p-chloroamphetamine by 5-HT neurones. Fluoxetine (10 mg/kg) caused a small but long lasting increase in current. Stimulation of the median raphe nucleus produced a marked and rapid rise in current in the hippocampus but a much smaller one in the striatum. This response could also be prevented by 24 h pretreatment with p-chlorophenylalanine (150 mg/kg). Seven days after p-chlorophenylalanine administration raphe stimulation again produced an increase in current. Rats under barbiturate anaesthesia showed no clear increase in current either after p-chloroamphetamine or raphe stimulation, indicating that barbiturates may affect neurotransmitter release. The results suggest that 5-HT release can be monitored in the freely moving unanaesthetized rat using in vivo voltammetry, and that a moderate decrease in brain 5-HT concentration leads to a substantial inhibition of drug or stimulation induced release of 5-HT.

Animals↗