Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 703 records · Page 39Linked to original sources

PubMed1984

How common is dementia in Parkinson's disease?

Current estimates suggest that about one in three patients with Parkinson's disease will become demented. Critical review of the studies on which this conclusion is based indicate that this figure is inflated. Errors in separating idiopathic Parkinson's disease from other causes of the akinetic-rigid syndrome, in differentiating dementia from confusional states, depression, and even normal ageing, and in defining and assessing dementia itself may have led to overestimation of the prevalence. A more conservative estimate is that one in five patients with Parkinson's disease is demented, but this assertion needs to be put to rigorous examination.

Aged↗

PubMed1984

Correlation of [3H]5-hydroxytryptamine (5HT) binding to brain stem preparations and the production and prevention of myoclonus in guinea pig by 5HT agonists and antagonists.

In guinea pig brain stem preparations [3H]5-hydroxytryptamine (5HT) bound specifically to both high and low affinity sites, but specific [3H]spiperone binding was low and could not be consistently detected. This indicates a prevalence of 5HT-1 type receptors in this tissue. High affinity-specific [3H]5HT binding was more potently displaced by indole-containing 5HT agonists than by piperazine-containing 5HT agonists. This agreed with the observation that indole-containing, but not piperazine-containing compounds induced dose-dependent myoclonus in guinea pigs which originates from brain stem. The capacity of indoleamine antagonists to displace [3H]5HT-specific binding from guinea pig brain stem was similar to their reported potency in displacing [3H]5HT from 5HT-1 receptors. The [3H]5HT-labelled binding site in guinea pig brain stem is a 5HT-1 receptor and appears to be responsible for the induction of indoleamine-dependent myoclonus.

Animals↗

PubMed1984

Enhancement of stereotypy induced by nomifensine in rats during continuous chronic haloperidol treatment.

Stereotyped behaviour induced by apomorphine (0.125 mg/kg s.c.) was inhibited in rats treated continuously for 20 months with haloperidol (1.4-1.6 mg/kg/day) while that induced by a higher dose of apomorphine (1.0 mg/kg s.c.) was enhanced. Stereotypy induced by nomifensine (3.125-25.0 mg/kg i.p.) was not inhibited at any dosage level in haloperidol-treated rats, and was enhanced by higher doses of nomifensine. The results indicate that the behavioural effects of endogenously released dopamine may not remain inhibited in rats undergoing chronic neuroleptic treatment.

Animals↗

PubMed1984

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p.) for 4 days induced dose-dependent parkinsonism in the common marmoset within 48 h. MPTP produced profound akinesia, rigidity of the trunk and limbs, postural abnormalities, loss of vocalization and, in some cases, postural tremor. In a single animal the administration of L-DOPA in conjunction with a peripheral decarboxylase inhibitor, reversed the parkinsonian symptoms. Subsequent biochemical analysis showed a profound loss of dopamine and [3H]dopamine uptake in the caudate-putamen, but no change in specific [3H]spiperone binding.

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

PubMed1984

Abnormalities in central motor pathway conduction in multiple sclerosis.

The technique of scalp stimulation of the motor cortex was used to demonstrate abnormalities in the corticomotoneuron pathway in multiple sclerosis. Unilateral or bilateral delays in corticomotoneuron conduction, dispersion of corticomotoneuron volleys, or both, were shown to occur in such patients. Changes may be seen even in patients with little clinical evidence of corticomotoneuron deficit.

Adult↗

PubMed1984

Duration of the first agonist EMG burst in ballistic arm movements.

In normal subjects, fast arm movements are accomplished by a diphasic or triphasic EMG activation of the agonist and antagonist muscles. The duration of the first agonist burst (Ag1) has been said to be constant for movements of different size, whilst its amplitude is variable. Previous studies focused on relatively small movements (10-40 degrees). We have studied the behaviour of the Ag1 duration over the full physiological range of wrist and elbow flexion movements in normal subjects. The results showed that the principle of invariance of Ag1 duration was true when small movements of about 15-30 degrees were studied, but when larger movements were made burst length increased. A similar increase in Ag1 burst duration also was seen during movements performed against a load and in contractions made with fatigued muscles. Changes in duration of the Ag1 burst appear to be part of the normal mechanism for increasing the impulsive force provided in rapid contractions.

Adult↗

PubMed1984

Repeated administration of N-methyl-4-phenyl 1,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurones.

N-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ( MPTP ) (10 mg/kg/day i.p.) was administered to rats for 16 days, which were then observed for a further 9-11 days. MPTP administration did not alter spontaneous locomotor activity or amphetamine (2.5 mg/kg ip)-induced locomotion. Apomorphine (0.25 mg/kg sc) did not alter locomotion in control rats but increased activity in MPTP treated animals. The stereotyped response to apomorphine (0.25 mg/kg sc) and amphetamine (2.5 and 5.0 mg/kg ip) was unaltered by MPTP administration. The striatal content of dopamine, HVA and DOPAC was unaltered by MPTP intake. The uptake of [3H]dopamine and [3H] 5HT in striatal synpatosomes was not changed by MPTP . The results suggest that MPTP , in the dose used, is not toxic to nigro-striatal dopamine neurones in the rat. This contrasts with its neurotoxic actions in monkeys and man.

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

PubMed1984

Movements not involved in posture are abnormal in Parkinson's disease.

We have studied movements of the top joint of the thumb in a group of patients with Parkinson's disease. Even when movements were performed with the proximal phalanx of the thumb clamped, and with the forearm fully supported, movement time was prolonged and multiple bursts of EMG activity were present in the flexor pollicis longus. An abnormality of such movements performed with complete external postural support suggests that disease of the basal ganglia affect all movements, not just those involved in posture.

Aged↗

PubMed1984

Functional increase in striatal dopaminergic activity following continuous long-term treatment with trifluoperazine.

Acute administration of trifluoperazine (2-10 mg/kg i.p.) caused a dose-dependent increase in potassium (K+)-evoked release of [3H]acetylcholine from striatal slices, but was without effect on K+-evoked release of [3H]glutamate. K+-evoked [3H]acetylcholine release was not different in striatal tissue from rats receiving 1 year's continuous administration of trifluoperazine (4.5-5.1 mg/kg/day) compared to age-matched control animals. However, K+-evoked striatal [3H]glutamate release was decreased in tissue from chronically trifluoperazine-treated animals compared to age-matched controls. The reversal of the acute action of trifluoperazine on striatal [3H]acetylcholine and the decrease of [3H]glutamate release on chronic administration is consistent with adaptive changes in striatal dopamine transmission during long-term neuroleptic treatment.

Acetylcholine↗

PubMed1984

5-Hydroxytryptamine (5-HT)-dependent myoclonus in guinea pigs is induced through brainstem 5-HT-1 receptors.

Myoclonic jerking in guinea pigs originates from the brainstem. Indole-containing 5-hydroxytryptamine (5-HT) agonists, but not piperazine-containing 5-HT agonists, induced myoclonus in guinea pigs at pharmacologically relevant doses. Guinea pig brainstem preparations possessed specific binding sites for [3H]5-HT but specific [3H]spiperone binding was low and inconsistent. 5-HT-1 receptors appear to predominate in this tissue. High affinity [3H]5-HT binding was potently displaced by indole-containing 5-HT agonists but only weakly displaced by piperazine-containing 5-HT agonists. The [3H]5-HT specific binding site in guinea pig brainstem responsible for the induction of indoleamine-dependent myoclonus has the characteristics of a 5-HT-1 receptor.

Animals↗

PubMed1984

Muscle spasms associated with Sudeck's atrophy after injury.

Four patients developed abnormal involuntary movements of a limb after injury. All subsequently developed sympathetic algodystrophy with Sudeck's atrophy and then abnormal muscle spasms or jerks of the affected limb, lasting years. Sympathetic block in three patients did not relieve the abnormal movements. Two patients obtained partial recovery spontaneously, but the other two required surgery for relief. The pathophysiology of this condition remains to be determined but the evidence suggests that it is a distinct, disabling clinical syndrome.

Adult↗

PubMed1984

Which motor disorder in Parkinson's disease indicates the true motor function of the basal ganglia?

Parkinson's disease in its earlier stages is argued to be the best available model for human basal ganglia dysfunction. The negative motor symptoms of Parkinson's disease are considered to give the greatest clue to normal function of this region of the brain. Particular attention is given to disorders of movement. These include delayed initiation and slowed execution of simple fast movements, due to abnormal specification of initial agonist activity. This might compromise predictive motor action, but this is shown to be preserved in Parkinson's disease. Disorders of more complex movements, such as repetitive, concurrent and sequential motor actions, are also abnormal in Parkinson's disease. These various defects are discussed in terms of a motor strategy involving the selection and sequencing of motor programmes to form a motor plan, and the initiation and execution of that motor plan. On the evidence available, it is suggested that patients with Parkinson's disease are unable to automatically execute learnt motor plans.

Basal Ganglia↗

PubMed1984

Gamma-aminobutyric acid and basal ganglia outflow pathways.

Neurons containing gamma-aminobutyric acid (GABA) are important outflow pathways from the striatum to the pallidal complex and substantia nigra. From these areas GABA-containing neurons pass to the thalamus and to various areas of the brainstem. Manipulation of GABA function in outflow zones in the rat can produce catalepsy, locomotor hyperactivity, stereotypy or circling behaviour, so mimicking the effect of altered dopamine function within basal ganglia. However, the behaviours produced by such manipulation do not form part of the animal's normal activities. Consequently manipulation of GABA action in the outflow zones of the basal ganglia may mimic extrapyramidal movement disorders more closely than the normal functions of these regions of the brain.

Animals↗

PubMed1984

Effects of motor cortex stimulation on spinal interneurones in intact man.

The effect of a descending corticospinal volley on a spinal inhibitory pathway, has been studied in five intact human subjects. Approximately 63% inhibition of the H-reflex evoked in wrist and finger flexor muscles, was produced by motor threshold stimulation of the radial nerve. When a submotor threshold cortical shock was given 2 to 4 ms before the H-reflex, this inhibition was reduced to approximately 38%. The timing of this effect is compatible with either a monosynaptic or disynaptic corticospinal tract projection onto the spinal inhibitory interneurone.

Electric Stimulation↗

PubMed1984

Behavioural effects mediated by unilateral nigral dopamine receptor stimulation in the rat.

Unilateral intranigral injections of dopamine in conscious rats pretreated with nialamide resulted in either ipsiversive or contraversive rotation depending upon the site of injection. Injection of dopamine (50 micrograms) into the zona compacta of the substantia nigra induced weak ipsiversive or mixed ipsiversive and contraversive rotation. Injection of dopamine (12.5-50.0 micrograms) into zona reticulata of substantia nigra induced only contraversive circling. Destruction of the ipsilateral medial forebrain bundle (MFB) using 6-hydroxydopamine (6-OHDA) abolished ipsiversive circling but enhanced contraversive circling produced by dopamine or apomorphine. The combination of a unilateral 6-OHDA lesion of MFB with a kainic acid or electrolesion of the ipsilateral strio-nigral and pallido-nigral pathways reduced contraversive circling to intranigral apomorphine (10 micrograms). Ipsiversive circling produced following intranigral injection of dopamine is dependent upon the integrity of ascending dopamine neurones. Contraversive rotation is independent of ascending dopamine pathways but is reliant upon afferent input to the substantia nigra from the striatum and/or globus pallidus.

Animals↗

PubMed1984

Enhanced GABA function in the angular complex (lateral periaqueductal grey matter and adjacent reticular formation) alters the postural component of striatal- or nigral-derived circling.

Unilateral injection of muscimol into the angular complex (lateral periaqueductal grey matter and adjacent reticular formation) caused ipsiversive rotation. Focal injection of picrotoxin into the same site produced contraversive rotation. Administration of apomorphine to animals with a unilateral 6-OHDA lesion of the left medial forebrain bundle caused contraversive rotation. Focal injection of muscimol into the angular complex reversed the direction of rotation such that apomorphine administration now produced ipsiversive circling. Unilateral injection of muscimol into substantia nigra zona reticulata caused contraversive rotation. Focal injection of picrotoxin into the same site produced ipsiversive rotation. The prior injection of muscimol into the ipsilateral angular complex prevented the contraversive rotation induced by intranigral administration of muscimol such that animals now showed ipsiversive circling. In both 6-OHDA-lesioned animals and animals receiving intranigral muscimol, focal injection of muscimol into the angular complex caused a reversal in the direction of circling through loss of the postural component with no obvious change in locomotor activity. Bilateral electrolytic lesions of the angular complex overall had no effect on amphetamine-induced locomotion. Manipulation of GABA function in the angular complex alters circling behaviour initiated from the striatum or substantia nigra by altering the postural component without affecting the locomotor response of the animals. The data suggest a critical role for the angular complex as an outflow station from basal ganglia.

Animals↗

PubMed1984

Differential effects of continuous administration for 1 year of haloperidol or sulpiride on striatal dopamine function in the rat.

Administration of haloperidol (1.4-1.6 mg/kg/day) for up to 12 months or sulpiride (102-109 mg/kg/day) for between 6 and 12 months increased the frequency of purposeless chewing jaw movements in rats. N,n-propylnorapomorphine (NPA) (0.25-2.0 mg/kg SC) did not induce hypoactivity in haloperidol-treated rats at any time; sulpiride treatment for 9 and 12 months caused a reduction in the ability of NPA to induce hypoactivity. Haloperidol, but not sulpiride, treatment enduringly inhibited low dose apomorphine effects (0.125 mg/kg SC). After 12 months, stereotypy induced by high doses of apomorphine (0.5-1.0 mg/kg) was exaggerated in haloperidol-, but not sulpiride-treated rats. Bmax for specific striatal 3H-spiperone binding was increased by haloperidol, but not sulpiride, treatment throughout the study. Bmax for 3H-piflutixol binding was not altered by chronic haloperidol or sulpiride treatment. Striatal dopamine-stimulated adenylate cyclase activity was inhibited for the 1st month of haloperidol treatment, thereafter returning to control levels; dopamine stimulation was increased after 12 months of sulpiride treatment. Striatal acetylcholine content was increased after 3 and 12 months of treatment with haloperidol, but was not affected by sulpiride. Chronic administration of sulpiride does not induce identical changes in striatal dopamine function to those caused by haloperidol.

Acetylcholine↗

PubMed1984

Differential alterations in striatal dopamine receptor sensitivity induced by repeated administration of clinically equivalent doses of haloperidol, sulpiride or clozapine in rats.

Rats received therapeutically equivalent doses of either haloperidol (1.7-1.9 mg/kg/day), sulpiride (112-116 mg/kg/day) or clozapine 30-35 mg/kg/day) continuously for 4 weeks. Treatment with haloperidol, but not sulpiride or clozapine, caused inhibition of stereotyped behaviour induced by apomorphine (0.125-0.25 mg/kg SC). Following drug withdrawal for up to 7 days, haloperidol and sulpiride, but not clozapine treatment caused an exaggeration of stereotyped behaviour induced by apomorphine. Bmax values for striatal 3H-spiperone binding were elevated in animals treated for 2 and 4 weeks with haloperidol, but not with sulpiride or clozapine. Following drug withdrawal, haloperidol, but not sulpiride or clozapine, treatment caused an increase in Bmax for striatal 3H-spiperone binding. Bmax values for striatal 3H-NPA binding revealed no change during haloperidol or clozapine treatment. Sulpiride treatment for 1 week caused an increase in Bmax for 3H-NPA binding, which returned to control levels at 2 and 4 weeks. Following drug withdrawal, there was an increase in Bmax for 3H-NPA binding in rats treated with haloperidol and sulpiride, but not clozapine. On continuous treatment and following withdrawal from haloperidol, sulpiride, or clozapine the ability of dopamine to stimulate striatal adenylate cyclase activity did not differ from that in control animals. Repeated administration of sulpiride or clozapine may not induce striatal dopamine receptor supersensitivity when given in clinically relevant doses, although haloperidol does.

Animals↗