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Biomedical subjects

C A Marsden

Publications and source records attributed to C A Marsden.

At least 181 records · Page 10Linked to original sources
PubMed1985

Increase in levels and ex vivo release of thyrotrophin-releasing hormone (TRH) in specific regions of the CNS of the rat by chronic treatment with antidepressants.

This study has investigated the effects of chronic treatment with amitriptyline, chlorimipramine, mianserin and metergoline on levels and ex vivo release of thyrotrophin-releasing hormone (TRH), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in specific regions of the brain and lumbar spinal cord of the rat. All four treatments caused a significant increase in levels of TRH in the lumbar spinal cord with amitriptyline producing the most marked effect. Amitriptyline alone caused a similar marked increase in levels of TRH in the nucleus accumbens and suprachiasmatic nucleus but none of the treatments had a significant effect on the TRH content of the median eminence or septal nuclei. Potassium-induced release of TRH and 5-HT ex vivo was measured from tissue slices of the nucleus accumbens, septal nuclei and lumbar spinal cord after treatment with amitriptyline and mianserin. An increase in release of TRH was observed only from tissue slices of areas where increased levels of the peptide had occurred; namely nucleus accumbens and lumbar spinal cord after administration of amitriptyline and lumbar spinal cord after mianserin. None of the drugs significantly altered the ex vivo release of 5-HT or 5-HIAA. The results are discussed in relation to a possible interaction between TRH and 5-HT receptors in the antidepressant action of these drugs.

Amitriptyline↗
PubMed1985

The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo.

K+-stimulated release of [3H]-5-hydroxytryptamine ( [3H]-5-HT) from rat frontal cortex slices was decreased by the 5-HT receptor agonists 5-methoxy-n1N-dimethyltryptamine and 5-methoxy-3(1,2,3,6,-tetrahydro-4-pyrindinyl)-1H-indole (RU-24969) (1 X 10(-5)M). RU-24969 (10 mg kg-1, i.p.) decreased extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection. The decrease in extracellular 5-hydroxyindoleacetic acid in vivo after RU-24969 (10 mg kg-1, i.p.) was also observed by in vivo voltammetry. The non-selective 5-HT antagonist metergoline prevented the RU-24969-induced decrease in 5-HT release and metabolism in vivo while the 5-HT2 receptor antagonist R-55669 (ritanserin) did not. The results support the view that RU-24969 stimulates a 5-HT1 receptor that is involved in the autoregulation of 5-HT release and metabolism.

Animals↗
PubMed1984

Differential pulse voltammetry: simultaneous in vivo measurement of ascorbic acid, catechols and 5-hydroxyindoles in the rat striatum.

This paper describes carbon fibre electrodes that can simultaneously monitor changes in ascorbic acid, dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in vivo in the rat striatum using differential pulse voltammetry. The separation between DOPAC and 5HIAA oxidation is improved and the size of the 5HIAA peak decreased by the removal of uric acid using the enzyme uricase indicating that uric acid oxidation may contribute to the oxidation peak at + 300 mV. Haloperidol (0.5 mg/kg) decreased ascorbic acid and 5HIAA but increased DOPAC and HVA while D-amphetamine (3 mg/kg) increased ascorbic acid, decreased DOPAC and HVA but had no effect on 5HIAA. These electrodes should be a useful means of investigating interactions between dopamine and serotoninergic systems in vivo.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Increased behavioural response to 5-methoxy-N,N-dimethyltryptamine but not to RU-24969 after intraventricular 5,7-dihydroxytryptamine administration.

Chemical lesioning of the 5-hydroxytryptamine neurones in the brain with 5,7-dihydroxytryptamine (200 micrograms i.c.v., 14 or 21 days previously) resulted in an enhanced behavioral response following administration of the 5-hydroxytryptamine receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg). The increase in the behavioural response showed a positive correlation with the decrease in whole brain 5-hydroxytryptamine levels. In contrast, there was no increase in the hyperlocomotion produced by the 5HT1 receptor agonist RU-24969 (3.5 mg/kg). The results are discussed in relation to the proposed 5-hydroxytryptamine receptor subtypes.

5,7-Dihydroxytryptamine↗
PubMed1984

Decrease in levels of thyrotrophin-releasing hormone (TRH) in the n. accumbens and lumbar spinal cord following repeated electroconvulsive shock.

The study investigated the effects of single and repeated electroconvulsive shock on levels and release of TRH in specific brain regions and thoracic and lumbar spinal cord. Whilst single electroconvulsive shock had no effect on TRH in any of the regions of the brain and spinal cord studied, repeated electroshock (5 shocks over 10 days and the rats killed 24 hr after the last shock) caused a significant decrease (-42 and -40% respectively) in levels of TRH in the nucleus accumbens and lumbar spinal cord. In the thoracic cord the level of TRH was also decreased after repeated electroshock but this did not reach significance. In contrast repeated electroshock had no significant effect on the content of TRH of the septal nuclei, hypothalamus, suprachiasmatic nucleus, or dorsal and medial raphe nuclei. Release of TRH was measured from slices prepared from nucleus accumbens and septal nuclei after repeated electroshock. A decrease in release was observed in nucleus accumbens with no effect in the septal nuclei. the results are discussed in relation to the possible interaction between dopaminergic and serotoninergic neurones and TRH in the antidepressant effects of electroconvulsive therapy.

Animals↗
PubMed1984

The TRH analogue CG3509 increases in vivo catechol/ascorbate oxidation in the N. accumbens but not in the striatum of the rat.

The effects of injection of the thyrotrophin-releasing hormone (TRH) analogue, orotyl-histidyl-proline amide (CG3509) into the accumbens and striatum, was studied on dopamine metabolism by means of in vivo voltammetry. Forty minutes after infusion of CG3509 (1-5 micrograms) into the n. accumbens there was a significant dose-related increase in the oxidation peak, corresponding to the oxidation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC) and ascorbic acid. The size of this peak returned to normal by 80 min after the infusion. There was no change in the indole oxidation peak. Infusion of CG3509 (5 micrograms) had no effect on the size of either the catechol or the indole oxidation peaks recorded in the striatum. Intraventricular injection of CG3509 (10 micrograms) also increased DOPAC/ascorbic acid oxidation peak recorded in the n. accumbens, without altering the indole peak. While the voltammetric technique used in the present experiments is not able fully to separate ascorbic acid and DOPAC in vivo, the results support the view that TRH and its analogues selectively increase dopaminergic activity in the mesolimbic region.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Analeptic effects of centrally injected TRH and analogues of TRH in the pentobarbitone-anaesthetized rat.

The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 micrograms total dose) and the analogues RX 77368 (0.01-1.0 microgram), CG 3509 (0.1-1.0 microgram), DN-1417 (1.0 microgram) and MK-771 (1.0 microgram) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 micrograms) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0-5.0 micrograms), RX 77368 (0.1-1.0 microgram) and CG 3509 (0.1-1.0 microgram) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 micrograms) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 microgram) and RX 77368 (0.1 microgram) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20-100 micrograms) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.

Anesthesia↗
PubMed1984

The effects of 5,7-dihydroxytryptamine and p-chlorophenylalanine on thyrotrophin-releasing hormone in regions of the brain and spinal cord of the rat.

The distribution of thyrotrophin-releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) were compared in ten regions of the rat brain and in lumbar spinal cord. After dissection, using a cutting box and tissue punches, TRH was measured by radioimmunoassay and 5-HT by HPLC with electrochemical detection. Within the brain the highest levels of TRH were found in the median eminence and the remaining hypothalamus. There were also relatively high levels in the suprachiasmatic nucleus, septal nuclei and nucleus accumbens. Highest levels of 5-HT were found in the raphe nuclei, hypothalamic nuclei, nucleus accumbens, stria terminalis, septal nuclei and hippocampus. 5,7-Dihydroxytryptamine (5,7-DHT; 200 micrograms, i.c.v.) markedly reduced levels of 5-HT in brain and spinal cord. In the ventral lumbar cord there was a comparable decrease of TRH and 5-HT (-80%) and a smaller but significant decrease in the nucleus accumbens (-55%) and septal nuclei (-38%). p-Chlorophenylalanine (PCPA; 250 mg/kg X 2) reduced levels of 5-HT (-80%), without significantly altering those of noradrenaline. p-Chlorophenylalanine also significantly reduced levels of TRH in the nucleus accumbens (-72%) but not in the other regions of brain or spinal cord taken. The results are discussed in relation to the previously described co-existence of TRH and 5-HT in the spinal cord and the possible alternative forms of interactions between amine and peptide in the nucleus accumbens.

5,7-Dihydroxytryptamine↗
PubMed1984

A comparison of the locomotor effects induced by centrally injected TRH and TRH analogues.

Thyrotrophin-releasing hormone (TRH) and its stable analogues CG3509 and RX77368 were injected directly into the nucleus accumbens, septum and striatum of the rat and locomotor activity was recorded. TRH (5-20 micrograms) caused a dose-dependent increase in locomotor activity when injected into the nucleus accumbens. TRH (20 micrograms) also increased locomotor activity after administration into the septum but not when put into the striatum. Both the TRH analogues (0.1 and 1.0 microgram) produced closely related increases in activity when injected into either the nucleus accumbens or septum but CG3509 was more potent with a longer lasting effect. Also, in contrast with TRH (20 micrograms), both TRH analogues stimulated locomotor activity when injected into the striatum at a dose of 1 microgram but the effect was less marked and delayed in onset compared to the nucleus accumbens and septum response. Dopamine (100 micrograms) injected into the accumbens or septum also produced significant increases in locomotor activity. The locomotor effects of the peptides are discussed in relation to a possible dopamine-mediated mechanism which contrasts with the actions of TRH and the analogues on barbiturate anaesthesia.

Animals↗
PubMed1984

Changes in monoamine metabolites measured by simultaneous in vivo differential pulse voltammetry and intracerebral dialysis.

A direct comparison has been made of the drug-induced changes in extracellular levels of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid measured using intracerebral dialysis and differential pulse voltammetry with carbon fibre electrodes. The comparison was carried out in chloral hydrate anaesthetized rats with a pretreated carbon fibre electrode implanted in one striatum and an intracerebral dialysis loop in the contralateral striatum. 3,4-Dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the dialysis perfusates were assayed by high pressure liquid chromatography with electrochemical detection. d-Amphetamine (2 mg/kg) decreased extracellular 3,4-dihydroxyphenylacetic acid and the height of the 3,4-dihydroxyphenylacetic acid oxidation peak, while haloperidol (0.5 mg/kg) increased 3,4-dihydroxyphenylacetic acid levels measured in the perfusates and the height of the 3,4-dihydroxyphenylacetic acid oxidation peak. In these experiments there were parallel changes in 3,4-dihydroxyphenylacetic acid levels and peak height and a close correlation between these changes. Tranylcypromine (10 mg/kg) produced an almost parallel decrease in extracellular 5-hydroxyindoleacetic acid (dialysis) and the height of the 5-hydroxyindoleacetic acid oxidation peak, with similar percentage changes and good correlation values being obtained. However, while 5-hydroxy-L-tryptophan (25 mg/kg) increased both the 5-hydroxyindoleacetic acid levels and the height of the 5-hydroxyindoleacetic acid oxidation peak, 5-hydroxyindoleacetic acid in the dialysis perfusates showed a greater increase than the oxidation peak. The results show a close correlation between changes in extracellular 3,4-dihydroxyphenylacetic acid and its respective voltammetric peak and strongly support the use of in vivo differential pulse voltammetry for monitoring dopamine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Hyperalgesia and the reduction of monoamines resulting from lesions of the dorsolateral funiculus.

Unilateral lesions of the dorsolateral funiculus (DLF) in the rat resulted in unilateral hyperalgesia as revealed by a hindpaw withdrawal test to heat. Larger lesions involving the dorsal column and ventrolateral quadrant did not cause hyperalgesia. The levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA) and dopamine (DA) were measured in the lumbar dorsal quadrant using high performance liquid chromatography (HPLC). In hyperalgesic animals DLF lesions caused an ipsilateral reduction of all the amines and a contralateral reduction of 5-HT and NA. This suggests that serotonergic and noradrenergic axons in the DLF give a contralateral innervation. A correlation was sought between the reduction of amine level and the degree of hyperalgesia shown by individual rats on lesioned and unlesioned sides of the cord. No consistent correlation was found with any of the amines.

Animals↗
PubMed1983

A manually-operated brain tissue slicer suitable for neurotransmitter release studies.

A simple, inexpensive device has been designed to prepare slices or prisms of brain tumor for metabolic and release experiments by means of a hand-operated method. It is particularly suitable for very rapid slicing of small, irregular pieces of brain tissue dissected from animals or specimens available at biopsy. This simple apparatus was produced as an alternative to the more widely used motor-driven tissue choppers. A comparison of the morphological and metabolic integrity of tissue produced by the new slicer and a conventional tissue chopper is presented. The hand tissue slicer has been used to measure the release of monoamine neurotransmitters and specific neuropeptides in vitro.

Animals↗
PubMed1983

In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine.

By using a new technique, intracerebral dialysis, in combination with high performance liquid chromatography and electrochemical detection, it was possible to recover and measure endogenous extracellular dopamine, together with its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) from the striatum and nucleus accumbens of anaesthetized or freely moving rats. In addition, measurements of extracellular 5-hydroxyindoleacetic acid, ascorbic acid, and uric acid were made. Basal extracellular concentrations of dopamine and DOPAC in the striatum were estimated to be 5 X 10(-8) M and 5 X 10(-6) M, respectively. d-Amphetamine (2 mg/kg s.c.) increased dopamine levels in the striatum perfusates by 14-fold, whereas levels of DOPAC and HVA decreased by 77% and 66%, respectively.

3,4-Dihydroxyphenylacetic Acid↗