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S Fleminger

Publications and source records attributed to S Fleminger.

10 recordsLinked to original sources
PubMed1992

Control of simultaneous movements distinguishes depressive motor retardation from Parkinson's disease and neuroleptic parkinsonism.

Patients with depressive motor retardation, neuroleptic induced parkinsonism or Parkinson's disease were tested on movement tasks requiring control of simultaneous movements. This was in order to determine whether these three groups of patients, who all show slowing of movements, also share the distinctive impairment of simultaneous movement control that is observed in Parkinson's disease. Though all three patient groups showed equivalent slowing on the motor tasks that were studied, the patterns of impairment were different. Only the patients with parkinsonism, either neuroleptic induced or from Parkinson's disease, showed additional slowing of a rapid ballistic elbow flexion movement when it was performed simultaneously with a rapid squeeze of the ipsilateral hand. Only patients with parkinsonism showed a significant increase in dual task interference on a bimanual bead and tapper task, compared with controls. The bead and tapper interference in patients with depressive motor retardation was between that of controls and parkinsonism. Having a bimanual skill had a large effect on the subjects' dual task interference on this task. The measures of dual task interference for the two tasks did not correlate with one another; difficulty running simultaneous motor programs does therefore not explain the interference that is observed when tapping is performed while the other hand simultaneously performs a dextrous motor task. Only patients with parkinsonism showed increased fatigue on the tapping task. The patients with depressive motor retardation did have elevated scores on a clinical rating of parkinsonism. Nevertheless there are clearly defined differences between the movement disorder observed in patients with depression, and that observed in in parkinsonism. The patterns of impairments in patients with neuroleptic parkinsonism were very similar to those of Parkinson's disease.

Adult↗
PubMed1992

Seeing is believing: the role of 'preconscious' perceptual processing in delusional misidentification.

We have no introspective knowledge of the effects of preconscious processing on our perceptions. We are, therefore, not aware that our expectancies may have prejudiced our perceptions. Expectancies tend to foster perceptions with which they are consonant. Therefore false expectations, driven by false beliefs, may result in misperceptions which reinforce those false beliefs. This morbid cycle is central to the delusional misidentification syndromes. This cycle, with positive feedback, is intrinsically unstable, which helps to explain brief episodes of delusional misidentification. Good sensory data, strong links between sense data and memory, and good judgement will all help to prevent misperceptions. The less these constraints are disrupted, the stronger will be the psychological forces needed to generate a delusional misidentification. It is likely that suspiciousness generates particularly assertive effects on preconscious processing of perceptions. Abnormalities of perceptual processing in patients with schizophrenia explain their proclivity to delusional misidentification.

Attention↗
PubMed1991

The relationship between the occupation of the D-1 dopamine receptor by [3H]piflutixol and the activity of dopamine-sensitive adenylate cyclase in rat striatal membranes.

The relationship between occupation of the D-1 dopamine receptor by [3H]piflutixol and inhibition of dopamine-sensitive adenylate cyclase has been studied. Experiments were performed in parallel; after the initial incubation to enable binding of [3H]piflutixol, half the tubes were assayed for [3H]piflutixol binding and the other half assayed for adenylate cyclase activity. The assay conditions for the two halves of the experiments were identical. (+/-)Sulpiride (3 x 10(-5)M) was present in all tubes to mask drug binding to the D-2 receptor. The inhibition of dopamine- (10(-3) and 10(-5)M) sensitive adenylate cyclase with increasing concentrations of [3H]piflutixol in the incubation mixture was compared to the saturation of specific [3H]piflutixol binding with those same concentrations of [3H]piflutixol. There was a linear relationship between receptor occupation by [3H]piflutixol and inhibition of dopamine sensitive adenylate cyclase. In a second experiment dopamine was present during the initial incubation with [3H]piflutixol. This resulted in a displacement of specific [3H]piflutixol binding and, as a consequence, a reduction of [3H]piflutixol's inhibition of dopamine-sensitive adenylate cyclase. In the absence of GTP in the initial incubation dopamine produced a greater reduction of [3H]piflutixol's inhibition of dopamine adenylate cyclase than displacement of specific [3H]piflutixol binding. In the presence of GTP in the initial incubation both displacement curves were shifted to the right, i.e. dopamine was less potent. However, under these conditions dopamine produced less inhibition of [3H]piflutixol's inhibition of dopamine adenylate cyclase than displacement of specific [3H]piflutixol binding. These results are interpreted as resulting from changes in D-1high and D-1low ratios as a result of incubation in the presence or absence of GTP.

Adenylyl Cyclase Inhibitors↗
PubMed1991

Left-sided Parkinson's disease is associated with greater anxiety and depression.

Seventeen patients with Parkinson's disease which was markedly asymmetric and worse on the right side of the body (RHP) were compared with 13 patients whose signs were worse on the left (LHP). The two groups of patients were well matched for age, duration of symptoms, disability, overall severity of signs, and medication. The mean scores on ratings of depression, using both a self-rating scale and semi-structured interview rating, were almost twice as great in the LHP group. The LHP group also had significantly more symptoms of anxiety. The prevalence of clinically significant psychopathology was increased about five fold in the LHP group compared with the RHP group. There was a close correlation between anxiety and depressive symptoms. The depression experienced by the patients was 'atypical', with relatively little anhedonia and evidence of a negative view of self, and prominent symptoms of anxiety. The best predictor of symptoms of depression and anxiety was a measure of social support and stress. They also correlated with the overall severity of Parkinson's disease.

Activities of Daily Living↗
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

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

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↗