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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 685 records · Page 38Linked to original sources
PubMed1985

Mesolimbic dopamine function is not altered during continuous chronic treatment of rats with typical or atypical neuroleptic drugs.

Rats were treated continuously for up to 20 months with either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day) or clozapine (24-27 mg/kg/day). Bmax for specific mesolimbic binding of 3H-spiperone, 3H-N, n-propylnorapomorphine or 3H-piflutixol did not differ in tissue taken from animals treated for up to 12 months with haloperidol, sulpiride or clozapine by comparison to age-matched control rats. Mesolimbic dopamine (50 microM)-stimulated adenylate cyclase activity was not altered in any drug treatment group. Spontaneous locomotor activity was transiently decreased during treatment with haloperidol for 1 or 3 months, but not by chronic sulpiride or clozapine treatment. Locomotor activity was not consistently increased in any drug treatment group. After 20 months of continuous drug treatment, focal bilateral application of dopamine (12.5 or 25 micrograms) into the nucleus accumbens caused equivalent increases in locomotor activity in control rats and in animals receiving haloperidol, sulpiride or clozapine. These findings suggest that dopamine receptor blockade is not maintained in the mesolimbic area following chronic treatment with haloperidol, sulpiride or clozapine, and indicate that, under these conditions, clozapine and sulpiride may not act selectively on mesolimbic dopamine receptors.

Adenylyl Cyclases↗
PubMed1985

Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function.

Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5-HT occurred at the onset of myoclonus, although tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p'-DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder.

Animals↗
PubMed1985

Comparison of the effects of benzodiazepines and other anticonvulsant drugs on synthesis and utilization of 5-HT in mouse brain.

Acute administration of clonazepam (0.5-8.0 mg/kg, i.p.), diazepam (2-32 mg/kg, i.p.), chlordiazepoxide (1-40 mg/kg, i.p.) or diphenylhydantoin (5-320 mg/kg, i.p.), caused a dose-related elevation of the concentrations of, 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan in whole mouse brain. Carbamazepine (5-100 mg/kg, i.p.), and phenobarbitone (10-80 mg/kg, i.p.) raised the concentrations of 5-HT and 5-HIAA in the brain, whereas flurazepam (5-80 mg/kg, i.p.) only elevated the level of 5-HIAA. After administration of L[G-3H]tryptophan (25 microCi, s.c.), clonazepam (4 mg/kg), diazepam (32 mg/kg, i.p.), chlordiazepoxide (40 mg/kg) or diphenylhydantoin (40 mg/kg), but not carbamazepine (50 mg/kg), flurazepam (40 mg/kg) or phenobarbitone (80 mg/kg), increased the content of labelled tryptophan in brain. However, administration of drugs did not alter the incorporation of the label into [3H]5-HT, suggesting that the synthesis of 5-HT was unaffected. When incorporation of [3H]tryptophan into [3H]5-HT was complete and the pool of labelled 5-HT was decreasing, clonazepam, diazepam, chlordiazepoxide and diphenylhydantoin elevated the content of [3H]5-HT in brain. Flurazepam, phenobarbitone and carbamazepine were without apparent effect. Calculation of the rate of utilization of 5-HT (Km) showed that all drugs, apart from flurazepam, reduced the utilization of 5-HT. Using the rate of disappearance of 5-HT after inhibition of tryptophan hydroxylase by p-chlorophenylalanine (PCPA), all drugs, except flurazepam, diphenylhydantoin and phenobarbitone, decreased the utilization of 5-HT. The major action of the anticonvulsant drugs on the function of 5-HT in brain appears to be a decrease in the utilization of 5-HT without altering synthesis.

Animals↗
PubMed1985

Behavioural effects in rats of unilateral and bilateral injections of opiate receptor agonists into the globus pallidus.

Unilateral injections of a putative kappa-opiate receptor agonist, ethylketocyclazocine, into the globus pallidus of rats caused dose-dependent ipsiversive circling which was inhibited by prior systemic administration of the opiate receptor antagonist naloxone. Neither a putative delta-opiate receptor agonist ( [D-Ala2, D-Leu5]enkephalin) nor a putative mu-opiate receptor agonist (Tyr-D-Ala-Gly-MePhe-Met(0)-ol) induced circling behaviour after unilateral intrapallidal injection. Bilateral intrapallidal injection of the delta-opiate receptor agonist or the mu-opiate receptor agonist caused an increase in locomotor activity which in both cases was reduced by systemic administration of naloxone. A specific delta-receptor antagonist, (N,N-bisalyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH) had no effect on the increase in locomotor activity caused by the delta-opiate receptor agonist. Bilateral intrapallidal injection of the kappa-opiate receptor agonist had no effect on locomotor activity. It is suggested that different opiate receptor subtypes within the globus pallidus differentially mediate circling and locomotor behaviour.

Animals↗
PubMed1985

The spectrum of cortical myoclonus. From focal reflex jerks to spontaneous motor epilepsy.

The purpose of this paper is to draw attention to the wide range of clinical motor phenomena which may be caused by abnormal sensorimotor cortical discharge. Eleven selected patients with cortical myoclonus are described. In all cases the brief muscle jerks appeared to involve cerebral cortical mechanisms, for there were enlarged cerebral evoked potentials to somatosensory or visual stimuli and (in 5 of the 6 cases investigated in this way) a time-locked cortical event preceded spontaneous or action-induced jerking. In some patients, cortical myoclonus occurred only in response to a variety of afferent inputs (cortical reflex myoclonus). In others, the myoclonus occurred only during movement, when cortical mechanisms were activated voluntarily (cortical action myoclonus), or the cortical discharge occurred spontaneously (spontaneous cortical myoclonus and epilepsia partialis continua), and even spread to cause focal motor epilepsy (Jacksonian seizures). Some patients showed combinations of stimulus sensitive and spontaneous myoclonus, epilepsia partialis continua, focal motor epilepsy and generalized grand mal seizures. Such variations probably represent subtle differences in the site of abnormality in sensorimotor cortical neuronal mechanisms.

Adolescent↗
PubMed1985

The anatomical basis of symptomatic hemidystonia.

Twenty-eight patients with focal (arm or leg) or hemidystonia due to tumour, arteriovenous malformation, infarction, haemorrhage or hemiatrophy are described. All had typical dystonic movements and/or postures, identical to those seen in idiopathic (primary) torsion dystonia. The site(s) of the lesion responsible, as defined by CT (computerized tomography) scan or pathological examination, was in the contralateral caudate nucleus, lentiform nucleus (particularly the putamen) or thalamus, or in a combination of these structures. Review of 13 other patients in the literature with hemidystonia and lesions defined by CT scan, and of 7 other patients with pathologically discrete lesions associated with hemidystonia, also indicated involvement of these structures. Dystonia may be due to abnormal input from thalamus to premotor cortex, due to lesions either of the thalamus itself, or of the striatum projecting by way of the globus pallidus to the thalamus.

Adolescent↗
PubMed1985

Pathophysiology of blepharospasm and oromandibular dystonia.

The pathophysiology of reflexes mediated by the fifth and seventh cranial nerves has been studied in 16 patients with blepharospasm and oromandibular dystonia compared with normal age-matched subjects. The EMG activity of the dystonic spasms in the periocular and jaw muscles was similar to that described in other muscles in patients with generalized torsion dystonia. The latency of the R1 and R2 components of the blink reflex and of the corneal reflex was normal. However, the amplitude and the duration of the R1 and R2 and the duration of the corneal reflex were increased. In some patients the R1 component was also present on the side contralateral to the stimulus, while in normal subjects it was present only on the ipsilateral side. The excitability cycle of recovery of the R2 component of the blink reflex after a prior conditioning shock was enhanced in the patients. There were no EEG potentials preceding blepharospasms in the patients, although a Bereitschaftspotential was seen beginning some 500 ms prior to voluntary blinks in the same individuals. Exteroceptive suppression in the contracting masseter and orbicularis oculi muscles was absent in 40 to 50 per cent of the patients. The jaw jerk was present in all the patients with normal latency. These results indicate that the neuronal arcs of the facial reflexes in blepharospasm and oromandibular dystonia are normal. However, there is an abnormal excitatory drive, perhaps from the basal ganglia, to the facial motoneurons and the interneurons which mediate the facial reflexes in the brainstem.

Adult↗
PubMed1985

Micturition disturbance in Parkinson's disease.

Ten men with longstanding idiopathic Parkinson's disease (IPD) were investigated by urodynamic and electromyographic methods. The urodynamic studies were repeated after stopping anti-Parkinsonian medication for several hours. All patients showed a difference between the two studies, but the changes were unpredictable. Three patients who had high residual urine volumes in both studies were thought to have prostatic obstruction. EMG analysis showed no evidence of a lower motor neurone lesion affecting the striated urethral sphincter. It was concluded that micturition difficulty in the patient with IPD is due to detrusor hyperreflexia, influenced by the basal ganglia, which is not associated with impaired striated urethral sphincter activity.

Adult↗
PubMed1985

Evidence that [3H]dopamine is taken up and released from nondopaminergic nerve terminals in the rat substantia nigra in vitro.

Potassium chloride (25 mM) and (+)-amphetamine (100 microM) both stimulated the release of radioactivity from slices of substantia nigra preincubated with [3H]3,4-dihydroxyphenylethylamine [( 3H]dopamine). Potassium chloride (25 mM) released radioactivity from slices of both zona compacta and zona reticulata. Prior 6-hydroxydopamine (6-OHDA) lesions of one nigrostriatal pathway did not reduce the spontaneous release of radioactivity, or the potassium chloride- or amphetamine-induced release of radioactivity from slices of nigra ipsilateral to the lesion after preincubation with [3H]dopamine. The accumulation of radioactivity following incubation of nigral slices from 6-OHDA-lesioned animals with [3H]dopamine was increased when compared to uptake into slices from intact tissue. In synaptosomal preparations of striatum, nomifensine but not desipramine or fluoxetine inhibited [3H]dopamine uptake. In contrast, nomifensine, desipramine, and fluoxetine all inhibited [3H]dopamine uptake in nigral synaptosomal preparations. Following 6-OHDA lesions of one nigrostriatal pathway the uptake of [3H]dopamine into nigral synaptosomal preparations was unchanged but uptake into striatal preparations was substantially decreased. In contrast, bilateral electrolesions of the dorsal and medial raphe nuclei reduced [3H]dopamine uptake into nigral preparations but not into striatal synaptosomes. The uptake of [3H]5-hydroxytryptamine ([3H]5-HT) into synaptosomal preparations of substantia nigra was abolished by fluoxetine and reduced by desipramine, but was unaffected by nomifensine. In contrast, fluoxetine, desipramine, and nomifensine all inhibited [3H]5-HT uptake into striatal synaptosomal preparations. Following 6-OHDA lesions of one nigro-striatal pathway the uptake of [3H]5-HT into nigral synaptosomal preparations was unchanged but uptake into striatal preparations was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1985

Properties of rat striatal D-2 dopamine receptors solubilized with the zwitterionic detergent CHAPS.

The specific binding of [3H]spiperone was determined in membrane preparations of rat striatum and following solubilization treatment with the zwitterionic detergent CHAPS. Membrane protein solubilization was confirmed by ultrafiltration, gel filtration and increased heat sensitivity. Specific binding of [3H]spiperone to the solubilized preparation was saturable and of high affinity, although solubilization led to an approximate 10 fold decrease in receptor affinity for [3H]spiperone. The drug displacement profile of binding to the CHAPS solubilized preparation corresponded to that of the dopamine D-2 receptor; binding was stereoselectively displaced by the isomers of butaclamol. The sodium dependence of sulpiride displacement of specific [3H]spiperone binding was retained in the CHAPS solubilized preparation. GTP (100 microM) only altered the ability of dopamine to displace [3H]spiperone binding to the solubilized preparation in the presence of 120 mM sodium chloride. The GTP effect was small compared with that observed in the membranes. Specific [3H]spiperone binding sites in the solubilized preparation were preferentially retained by a wheat germ agglutinin affinity column and subsequently eluted with N-acetyl-D-glucosamine. Gel filtration of the solubilized preparation using a Sepharose column resulted in two peaks of specific [3H]spiperone binding, the larger component had a Stokes radius of 7.7 nm. CHAPS treatment of rat striatal membranes results in solubilization of the D-2 receptor in an active form. The D-2 site appears to be a glycoprotein of high molecular weight.

Adsorption↗
PubMed1985

Writing tremor: its relationship to benign essential tremor.

Nine patients with tremor on writing and one patient with tremor only on swinging a golf club were investigated. None of the patients had any other neurological symptoms or signs. The frequency of the tremor ranged from 5 to 6 Hz. Rapid passive supination or pronation of the forearm by a torque motor evoked a short burst of alternating tremor in seven patients. The tremor was improved by alcohol or propranolol in six patients. These characteristics of writing tremor (and of other isolated action tremors) suggest that it is a variant of benign essential tremor.

Adult↗
PubMed1985

Validity and reliability of a rating scale for the primary torsion dystonias.

For quantitative assessment of the primary torsion dystonias, a rating scale is proposed that has two sections--a Movement Scale, based on examination, and a Disability Scale, based on the patient's statements about seven activities of daily living. We assessed the validity of the Movement Scale by comparing scores with a ranking of patients according to dystonia severity and with ratings of the patients on the Disability Scale. In addition, we assessed the inter-and intra-rater reliability of the scale by comparing independent scorings of patients by four examiners and by comparing scorings by the same examiners performed at different times. We found that the Movement Scale was a valid and reliable indicator of the severity of primary torsion dystonia.

Activities of Daily Living↗
PubMed1985

Lisuride in dystonia.

Lisuride hydrogen maleate, 0.4 to 5 (mean, 3) mg/d, was given orally to 42 subjects with various types of dystonia. In seven of the eight patients who improved (one with segmental dystonia, one with myoclonic dystonia, two with spasmodic torticollis, two with cranial dystonia, and two with tardive dystonia), the response was confirmed by double-blind placebo substitution. No patients with a suspected structural brain lesion improved. There was no consistent pattern of response among those patients with different forms of idiopathic (primary) dystonia. Lisuride improved some patients, but had no effect on other, apparently identical, patients.

Administration, Oral↗
PubMed1985

The corneal reflex and the R2 component of the blink reflex.

A reflex contraction of the human orbicularis oculi muscles can be evoked by stimulation of either the supraorbital region ("blink reflex") or the cornea ("corneal reflex"). We found that the latency of the corneal reflex was longer, and the duration was longer than the R2 component of the blink reflex. The absolute refractory period of the R2 component of the blink reflex was longer after supraorbital than after corneal conditioning stimulation. When the R2 component of the blink reflex was habituated by repetitive stimuli, stimulation of the cornea still evoked a reflex, but supraorbital stimulation produced only a depressed R2 response. These findings suggest that the two reflexes do not have identical neural connections.

Adult↗
PubMed1985

Stretch reflex blepharospasm.

We studied a patient with blepharospasm provoked by stretching the orbicularis oculi muscles. With the eyes closed, EMG of the orbicularis oculi at rest revealed spontaneous rhythmic muscle activity that was not visible. When she tried to open her eyes, repetitive jerking blepharoclonus and tonic blepharospasm rendered her functionally blind. Passive stretching of the orbicularis oculi evoked a burst of EMG activity with two components. Touch or pinprick did not elicit such reflex activity. Anesthesia of the supraorbital nerves abolished muscle responses to stretch and improved the blepharospasm.

Aged↗
PubMed1984

The binding of [3H]N-(chloroethyl)-norapomorphine to rat striatal membranes.

N-(chloroethyl)-norapomorphine (NCA) irreversibly inhibits striatal dopamine function, the binding of dopamine agonist ligands and dopamine-stimulated adenylate cyclase. A selective interaction of [3H]NCA with dopamine receptor sites would be of use in the characterisation and isolation of brain dopamine receptors. In this study the binding of [3H]NCA to homogenates of rat striatum was investigated. Binding of [3H]NCA to striatal preparations was saturable and irreversible and prevented with high affinity by dopamine agonist drugs with a catechol moiety. However, binding was not prevented in a stereoselective manner by the isomers of butaclamol, flupenthixol or sultopride. Nor was [3H]NCA binding specific to brain areas containing dopamine receptors. We conclude that [3H]NCA binding is not selective for dopamine receptors, although NCA inhibited both [3H]N,n-propylnorapomorphine (NPA) and [3H]spiperone binding in a non-competitive manner.

Amisulpride↗