Search PubMed⌕ Search

Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 667 records · Page 37Linked to original sources
PubMed1986

Urea-induced stimulus-sensitive myoclonus in the rat.

Uremia in humans can cause spontaneous and stimulus-sensitive myoclonus that responds to clonazepam. Uremic myoclonus in humans resembles the reticular reflex form of postanoxic action myoclonus. Previous investigations have established that urea infusions in the cat can produce spontaneous and stimulus-sensitive myoclonus. This has been shown, electrophysiologically, to arise in the brainstem medullary reticular formation, and it does not require forebrain structures. Our own studies in the rat have shown that urea infusions also produce spontaneous and stimulus-sensitive myoclonus. Electrophysiologically, this resembles human reticular reflex myoclonus. It can be reduced by clonazepam. The myoclonus produced by urea infusions in the rat progresses very rapidly into uncontrollable tonic-clonic convulsions. Although the urea model in the rat mimics some forms of human myoclonus that arise in the brainstem, it is not suitable as a routine animal model for pharmacological investigations.

Animals↗
PubMed1985

Increase of the Bereitschaftspotential in simultaneous and sequential movements.

The amplitude and duration of the Bereitschaftspotential were analysed in 9 normal subjects prior to four different motor tasks: (1) simple isotonic elbow flexion ('flex'), (2) simple isometric finger flexion ('squeeze'), (3) simultaneous performance of 'flex' and 'squeeze', and (4) sequential performance of 'flex' then 'squeeze'. The Bereitschaftspotential was much larger and slightly longer in the simultaneous and sequential movements than in the same movements performed separately. The amplitudes of the Bereitschaftspotential were measured 150 and 75 ms prior to electromyographic (EMG) onset of the prime mover, and at the time of EMG onset. Changes in size were seen in all leads (FCz, Cz, C3', C4') and at all time points. It is suggested that the increase of the Bereitschaftspotential prior to complex arm movements reflects a greater activation of the supplementary motor area before simultaneous and sequential movements.

Adult↗
PubMed1985

The toxic actions of MPTP and its metabolite MPP+ are not mimicked by analogues of MPTP lacking an N-methyl moiety.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite 1-methyl-4-phenylpyridine (MPP+) and three analogues of MPTP, lacking an N-methyl moiety, namely, 4-phenylpiperidine (I), 4-phenyl-1,2,3,6-tetrahydropyridine (II) and 4-phenylpyridine (III), were infused continuously for a period of 4 days into the rat substantia nigra. Within 12 h of commencing the bilateral infusion of MPTP or MPP+, rats showed marked motor deficits with reduction in locomotor activity, loss of ability to move the forelimbs and grip with forepaws and, following MPP+ infusions, similar loss of movement in the hindlimbs associated with the development of limb and body rigidity. These motor deficits were not induced by the 3 analogues of MPTP on infusion into the substantia nigra. After 4 days of infusion, the motor deficits caused by MPTP and, in particular, MPP+, were still marked, and for MPP+ these correlated with marked loss of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. 4-Phenyl-1,2,3,6-tetrahydropyridine caused a small loss in striatal DA and DOPAC, but the other analogues failed to modify the striatal content of DA or its metabolites. Small alterations of chemical structures related to MPTP and its metabolite can critically alter ability to induce behavioural and neurochemical changes reflecting toxicity on the nigrostriatal DA system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

The effects of dopamine and dopamine agonists on the release of 3H-GABA and 3H-5HT from rat nigral slices.

Only high micromolar concentrations of dopamine and dopamine agonists altered spontaneous and KCl-evoked release of 3H-GABA and 3H-5HT from rat nigral slices in vitro. Apomorphine (100 microM) and dopamine (100 microM) enhanced the spontaneous release of 3H-5HT but the effect of dopamine was not reversed by haloperidol (1 microM). Both apomorphine (100 microM) and dopamine (100 microM) enhanced the KCl-evoked release of 3H-5HT but these effects were not reversed by haloperidol (1 microM). Apomorphine (10-250 microM) and dopamine (10-250 microM) inhibited 3H-5HT uptake into nigral synaptosomal preparations in a concentration-dependent manner. Accordingly, a major portion of the apparent effect of these drugs on 3H-5HT release may be due to inhibition of 3H-5HT uptake. Dopamine (100 and 1000 microM), amphetamine (100 microM), apomorphine (100 microM) and 2-amino-6,7-dihydroxytetralin (ADTN; 100 microM) were without effect on the spontaneous release of 3H-GABA from nigral slices. Apomorphine (100 microM) and ADTN (100 microM) reduced the KCl-evoked release of 3H-GABA from substantia nigra, an effect antagonized by haloperidol (1 microM). However, amphetamine (100 microM) and dopamine (100-1000 microM) were without effect on KCl-evoked 3H-GABA release. These results suggest that only high concentration of some dopamine agonists can modulate 3H-5HT and 3H-GABA release in substantia nigra. However, dopamine either had no effect, or its actions were not reversed by dopamine receptor blockade, so it appears unlikely that dendritic dopamine release will influence GABA and 5HT release in substantia nigra.

Animals↗
PubMed1985

Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat.

Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' treatment with clozapine (24-27 mg/kg/day). Apomorphine-induced (0.125-0.25 mg/kg) stereotyped behaviour was inhibited during 12 months treatment with haloperidol. Clozapine treatment was without effect. After 12 months, stereotypy induced by higher doses of apomorphine (0.5-1.0 mg/kg) was enhanced in haloperidol, but not clozapine, treated rats. Bmax for striatal 3H-spiperone binding was elevated throughout 12 months of haloperidol administration, but was not altered by clozapine treatment. Bmax for striatal 3H-NPA binding was only elevated after 12 months of haloperidol treatment; clozapine treatment was without effect. Bmax for 3H-piflutixol binding was not altered by haloperidol treatment, but was increased after 9 and 12 months of clozapine treatment. Dopamine (50 microM)-stimulated adenylate cyclase activity was inhibited after 1 month's haloperidol treatment but normal thereafter. Adenylate cyclase activity was not altered by chronic clozapine treatment. Striatal acetylcholine content was increased after 3 and 12 months of haloperidol or clozapine intake. These findings indicate that the chronic administration of the atypical neuroleptic clozapine does not produce changes in brain dopamine function which mirror those of the typical neuroleptic haloperidol. In particular, chronic administration of clozapine, unlike haloperidol, does not appear to induce striatal D-2 receptor supersensitivity. Unexpectedly, clozapine treatment, unlike haloperidol, altered D-1 receptor function.

Acetylcholine↗
PubMed1985

The neurotoxic actions of 1-methyl-4-phenylpyridine (MPP+) are not prevented by deprenyl treatment.

1-Methyl-4-phenylpyridine (MPP+) injected into the cerebral ventricles (ICV) of mouse caused depletions of striatal dopamine (DA)(-42%), 3,4-dihydroxyphenylacetic acid (DOPAC) (-34%) and homovanillic acid (HVA) (-16%) content without significant reductions in levels of noradrenaline (NA), serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA). When deprenyl was administered before MPP+, striatal DA and its metabolites were further depleted, and striatal NA and 5-HT levels also were reduced. Further, whilst ICV MPP+ alone failed to influence the biochemistry of the limbic areas (nucleus accumbens plus tuberculum olfactorium), in the presence of deprenyl MPP+ caused 20-40% reductions in levels of limbic NA, DA, DOPAC, HVA, 5-HT and 5-HIAA. Therefore, deprenyl treatment does not prevent the neurotoxic actions of MPP+; indeed, a more extensive neurotoxicity for MPP+ is revealed in the presence of this monoamine oxidase inhibitor.

1-Methyl-4-phenylpyridinium↗
PubMed1985

Acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine affects the adrenal glands as well as the brain in the marmoset.

A parkinsonian syndrome was induced in marmosets by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 days. Ten days following the onset of drug administration, brainstem and adrenal tissues were assayed for levels of monoamines and their metabolites. In the brainstem tegmentum, dopamine, its metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), and noradrenaline were reduced, whereas 5-hydroxytryptamine (5-HT) levels were elevated, in comparison with untreated controls. In the adrenal gland, 5-HT and adrenaline levels were unchanged, but dopamine and noradrenaline were substantially elevated.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

The dopamine D2 agonist LY 141865, but not the D1 agonist SKF 38393, reverses parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset.

Marmosets treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p. daily for up to 8 days) develop profound parkinsonian akinesia. Administration of the D1 agonist SKF 38393 (1-20 mg/kg i.p.) 4-6 weeks later had no effect on the motor activity of animals pretreated with MPTP. In contrast, the administration of the D2 agonist LY 141865 (0.1 or 0.5 mg/kg i.p.) caused a marked increase in motor activity lasting for up to 2 h. We conclude that stimulation of D2 dopamine receptors is essential for motor activation of parkinsonian marmosets and that D1 stimulation alone is not sufficient to overcome the akinesia induced by MPTP treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

SCH 23390 may alter dopamine-mediated motor behaviour via striatal D-1 receptors.

SCH 23390 potently displaced the specific binding of 3H-piflutixol to D-1 sites in striatal membranes but haloperidol was only weakly effective. SCH 23390 weakly displaced specific 3H-spiperone binding to D-2 sites, but haloperidol was potent. SCH 23390 was more effective than haloperidol in inhibiting dopamine stimulated striatal adenylate cyclase activity. These results confirm the D-1 selectivity of SCH 23390. However, SCH 23390 inhibited apomorphine-induced stereotypy and climbing behaviour in rats with equal potency to haloperidol. Haloperidol dose-dependently increased striatal HVA and DOPAC concentrations without altering dopamine content. Low doses of SCH 23390 elevated striatal DOPAC concentrations but higher doses were without effect; striatal dopamine and HVA overall was unaffected by administration of SCH 23390. Haloperidol did not affect basal 3H-acetylcholine release from striatal slices but reversed the apomorphine-induced inhibition of 3H-acetylcholine release. SCH 23390 did not affect basal 3H-acetylcholine release nor did it reverse the apomorphine-induced inhibition of 3H-acetylcholine release. The ability of SCH 23390 to inhibit motor behaviour in the rat may be due to its action on D-1 receptors since the drug does not cause typical changes in parameters of striatal D-2 receptor function.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Lack of effect of intranigral administration of a dopamine analogue, (+/-)-3-(3-hydroxyphenyl)-N,n-propylpiperidine [(+/-)-3-PPP], on nigrostriatal dopamine neurones.

Bilateral injection of apomorphine into the zona reticulata of substantia nigra in rats reduced locomotor activity and striatal dopamine (DA) turnover. In contrast, bilateral injection of (+/-)-3-(3-hydroxyphenyl)-N,n-propylpiperidine [(+/-)-3-PPP] into the zona reticulata (ZR) did not reduce locomotor activity and did not affect striatal DA turnover. A high dose of (+/-)-3-PPP increased locomotor activity. Unilateral injection of (+/-)-3-PPP, but not of apomorphine, into the ZR induced a brief period of contraversive rotation. (+/-)-3-PPP may not alter nigral DA autoreceptor function but may interact with DA receptors located on non-dopaminergic nigral neurones.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Domperidone.

Explore the source record for details and available documents.

Domperidone↗
PubMed1985

Differential alteration of striatal D-1 and D-2 receptors induced by the long-term administration of haloperidol, sulpiride or clozapine to rats.

Rats received haloperidol, sulpiride, or clozapine in their daily drinking water for up to 1 year in clinically equivalent doses. After 12 months' drug intake, and while drug administration continued, striatal dopamine function was assessed. Haloperidol induced D-2 receptor hypersensitivity as shown by enhanced apomorphine-induced stereotypy, elevated Bmax for specific 3H-spiperone and 3H-NPA binding, and an increase in striatal acetylcholine content. D-1 receptor sites appeared unaffected, since dopamine-stimulated adenylate cyclase and specific 3H-piflutixol binding were not altered. In contrast, neither sulpiride nor clozapine enhanced apomorphine-induced stereotypy or increased Bmax for 3H-spiperone binding. Sulpiride, but not clozapine, increased Bmax for 3H-NPA binding; clozapine, but not sulpiride, elevated striatal acetyl choline concentrations. In general, both sulpiride and clozapine enhanced D-1 function as assessed by dopamine-stimulated adenylate cyclase or 3H-piflutixol binding. On acute administration sulpiride and clozapine appear to act at D-2 sites, but continuous chronic administration of these compounds does not result in the development of striatal D-2 receptor hypersensitivity. The absence of change in D-2 function during chronic treatment, coupled with an ability to enhance D-1 function, may contribute to the low incidence of tardive dyskinesia produced by these drugs in man.

Animals↗
PubMed1985

Is tardive dyskinesia a unique disorder?

The role of neuroleptics in causing the tardive dyskinesia syndrome is controversial. To properly assess the contribution of drugs as the etiology of dyskinesias, the effects of aging, the natural history of psychosis, and characteristics of spontaneous dyskinesias must be considered. Though the buccolinguo-masticatory triad is seen more often in tardive than in spontaneous dyskinesias, these two disorders have many symptoms in common. Other dyskinesias, such as idiopathic and tardive dystonia or tardive Tourette's syndrome and dyskinesias in untreated schizophrenia, are poorly understood. Chronic neuroleptic treatment may only precipitate TD in those already predisposed to develop such movement disorders. Tardive dyskinesia is not a unique movement disorder, but rather spans several clinical and epidemiological phenomena which must be considered in a balanced evaluation of how much of the permanent dyskinesias should be attributed to neuroleptic drugs.

Antipsychotic Agents↗
PubMed1985

Cerebral potentials and electromyographic responses evoked by stretch of wrist muscles in man.

The cerebral evoked potential produced by rapid extension of the wrist was recorded from scalp electrodes in normal subjects while they exerted a small background flexor torque (0.24 Nm) against an electric motor. The initial part of the response consisted of a negative deflection (N1) with an average latency of 24.7 ms. This was followed by a biphasic P1/P2 (32 ms) response and a large later negative wave (N2) (76 ms). Passive wrist extension also evoked reflex EMG responses in the forearm flexor muscles which could be resolved into a short latency (25 ms) and long-latency (52 ms) component. The cerebral responses persisted almost unchanged during complete ischaemic anaesthesia of the hand produced by a pressure cuff around the wrist, and were reduced if the stretch was given during voluntary wrist flexion. The primary component (N1-P1/P2) of the cerebral response probably represents the arrival at the cortex of the muscle afferent volley. However, the significance of the secondary component (P1/P2-N2) is unknown. Under certain conditions, its size was related to the size of the long latency stretch reflex evoked by stretch of the flexor muscles. Thus, increasing the velocity of stretch or decreasing the repetition rate (from 1.0 to 0.15 Hz) at which stretches were applied, increased the size of both the muscle reflex and the cerebral response. The secondary component also could be changed by voluntary reaction to wrist stretch. Changes in the size of the secondary component of the evoked response may represent the earliest cortical sign of interaction between sensory input and motor output.

Adult↗
PubMed1985

Pharmacological characterisation of spontaneous or drug-associated purposeless chewing movements in rats.

Continuous administration of haloperidol, sulpiride, or cis-flupenthixol, but not of domperidone or apomorphine, to Wistar rats for up to 3 weeks caused an increase in spontaneous purposeless chewing movements. Treatment with physostigmine and pilocarpine, but not neostigmine, for up to 3 weeks increased chewing, whilst scopolamine decreased chewing. Metergoline and cyproheptadine, but not quipazine, increased chewing after only 1 and 7 days but not thereafter. Chewing was not altered following treatment with compounds acting on GABA or noradrenaline systems or by a range of non-neuroleptic agents inducing dystonia in man. The enhancement of chewing induced by neuroleptic and cholinomimetic drugs was reduced by acute treatment with scopolamine, and reverted to control levels following drug withdrawal. Neuroleptic-induced purposeless chewing in Wistar rats appears to be primarily influenced by cerebral dopamine and acetylcholine function and may resemble acute dystonia, rather than tardive dyskinesia.

Acetylcholine↗
PubMed1985

Effects of discontinuous drug administration on the development of dopamine receptor supersensitivity during chronic trifluoperazine or cis-flupenthixol administration to rats.

Rats received continuous or discontinuous administration of trifluoperazine or cis-flupenthixol in drinking water for up to 12 months. Continuous and discontinuous trifluoperazine administration had no consistent effect on apomorphine-induced stereotyped behaviour and there was no difference between drug treatments. Continuous and discontinuous cis-flupenthixol administration enhanced apomorphine-induced stereotypy, but there was no difference in the effect of the two drug treatments. Both continuous and discontinuous administration of trifluoperazine increased the number of specific striatal 3H-spiperone binding sites (Bmax). Over the period of treatment there was no difference in the effects of the different treatments. Continuous or discontinuous cis-flupenthixol intake did not increase Bmax after 6 or 12 months intake. Continuous or discontinuous neuroleptic treatment produced no difference in functional striatal dopamine receptor activity as judged by apomorphine-induced stereotyped behaviour. Ligand binding studies also suggest that the overall change in striatal receptor function is not affected by the use of a discontinuous drug regime.

Animals↗