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Biomedical subjects

S Rose

Publications and source records attributed to S Rose.

At least 217 records · Page 12Linked to original sources

Increased caudate dopamine turnover may contribute to the recovery of motor function in marmosets treated with the dopaminergic neurotoxin MPTP.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets initially impaired motor function, but a partial recovery occurred over the following weeks. At both 10 days and 4-6 weeks following MPTP treatment, [3H]dopamine ([3H]DA) uptake into synaptosomal preparations of putamen was markedly decreased. At 10 days and 4-6 weeks following MPTP treatment DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the caudate nucleus and nucleus accumbens were substantially reduced. However, the levels of HVA and DOPAC in caudate nucleus were higher at 4-6 weeks than at 10 days. The ratio of (DOPAC + HVA)/DA in caudate nucleus was elevated at 10 days following MPTP treatment and even more so at 4-6 weeks. No change in Bmax or Kd values for [3H]spiperone binding to caudate preparations were observed. The recovery of motor function in marmosets observed following MPTP treatment may result partially from a compensatory increase in caudate DA turnover by remaining neurones.

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

Further treatment with MPTP does not produce parkinsonism in marmosets showing behavioural recovery from motor deficits induced by an earlier exposure to the toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually recovered normal motor function. Further treatment consisted of a cumulative dose of MPTP of 78-83 mg/kg (i.p.) but this produced only modest akinesia. At 12-18 months after the initial treatment with MPTP, the content of dopamine, HVA and DOPAC in the caudate and putamen was markedly reduced. However, levels of dopamine, HVA and DOPAC in the nucleus accumbens were normal. Three months after the second treatment with MPTP there was no further decrease in the content of dopamine in the caudate-putamen. However, in the nucleus accumbens the content of dopamine, HVA and DOPAC was now reduced. The initial treatment with MPTP substantially decreased the binding of [3H]mazindol in the caudate-putamen but less so in the nucleus accumbens. Only a small additional decrease occurred upon further treatment with MPTP. The density of tyrosine hydroxylase (TH) immunoreactive cells in substantia nigra was reduced after the initial treatment with MPTP. However, the cell loss was far less marked than the decrease in terminal density, assessed by the binding of [3H]mazindol. Subsequent treatment with MPTP caused a small further loss of tyrosine hydroxylase-positive cells. Initial treatment with MPTP may kill the majority of MPTP-sensitive dopamine cells in the nigra. Compensation by the remaining nigrostriatal neurones may account for the behavioural recovery observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Treatment with a selective MAO B inhibitor prevents loss of dopamine in the nucleus accumbens of MPTP-treated common marmosets.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced motor deficits, associated with a marked decrease in the uptake of [3H]dopamine into synaptosomes in the putamen and a reduction in the content of dopamine in both caudate nucleus and nucleus accumbens. Histological analysis showed a marked loss of dopamine-containing cells in the zona compacta of the substantia nigra and less loss in the ventral tegmental area. Treatment of animals with the selective monoamine oxidase (MAO) B inhibitor, MDL 72145 (0.5 or 2.0 mg/kg) prior to, during and following administration of MPTP partially protected animals from the motor abnormalities induced by administration of MPTP alone. Both doses inhibited the onset of akinesia but only the large dose of MDL 72145 prevented the occurrence of other motor abnormalities. Moreover, while MDL 72145 (2.0 mg/kg) prevented the loss in uptake of [3H]dopamine into synaptosomes of the putamen, this was only partly prevented using the smaller dose. Similarly, while MDL 72145 (2.0 mg/kg) prevented loss of dopamine in the caudate, only partial protection was afforded by the smaller dose. However, in the nucleus accumbens, both doses of MDL 72145 prevented the depletion of dopamine, occurring in this region. Histological examination of the substantia nigra showed little or no cell loss in animals receiving the larger dose of MDL 72145 but a moderate cell loss in animals receiving the smaller dose. No damage was observed in the ventral tegmental area of animals treated with MDL 72145 (2.0 mg/kg) and only mild cell loss in those receiving the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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

The effect of carbidopa on plasma and muscle levels of L-dopa, dopamine, and their metabolites following L-dopa administration to rats.

Administration of L-dopa (L-3,4-dihydroxyphenylalanine) (200 mg/kg p.o.) to rats produced elevated plasma and muscle concentrations of both L-dopa and 3-O-methyldopa (3-OMD). This effect was potentiated by simultaneous administration of carbidopa (25 mg/kg p.o.). Both L-dopa and 3-OMD accumulated in muscle after administration of L-dopa with or without carbidopa. Elevated dopamine levels were detected in both muscle and plasma after treatment with L-dopa alone. Concurrent administration of carbidopa only diminished dopamine levels in plasma, and the duration of raised dopamine levels in muscle was increased. Carbidopa administration had no effect on the elevated plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) caused by L-dopa administration. In muscle, carbidopa treatment tended to prolong the duration of raised metabolite levels. Muscle appears to accumulate L-dopa at a site where decarboxylation is not totally prevented by concurrent carbidopa administration, and where dopamine is not degraded as actively as in other tissues. The muscle sink for L-dopa may influence the plasma profile of the amino acid, which has implications for the therapeutic response to L-dopa in Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

Levels of Met-enkephalin, Leu-enkephalin, substance P and cholecystokinin in the brain of the common marmoset following long term 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine treatment.

Common marmosets were treated daily with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 7-9 mg/kg i.p.) for 25 days, and then kept out of drug for three months before biochemical measurements in various brain areas. This treatment induced a dramatic fall (-80%) in dopamine, homovanillic acid and dihydroxyphenylacetic acid levels in the putamen and caudate nucleus, and a significant but less pronounced reduction (less than or equal to 50%) in the levels of these compounds in the nucleus accumbens. In contrast, the concentrations of four neuropeptides: met-enkephalin, leu-enkephalin, substance P, and cholecystokinin, remained unaltered in all brain areas examined in MPTP-treated marmosets. Therefore the neuropeptide alterations previously reported in Parkinson's disease are probably not secondary to the severe lesion of dopaminergic neurones, but constitute another intrinsic feature of the disease.

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

The effects of social context and verbal skill on the stereotypic and task-involved behaviour of autistic children.

Twelve autistic children's rates of Stereotypy, Task Involvement and Non Involvement were observed in three settings representing levels of interpersonal contact: Individual Attention, Group Attention and Play. The children were assigned in two groups reflecting high and low verbal skills and overall level of autistic disturbance was used as a covariate. Results showed that the highest levels of Task Involvement and the lowest levels of Stereotypy and Non Involvement were associated with the highest level of interpersonal contact. Verbal skill level predicted higher rates of prosocial behaviour overall, and interacted with the setting measures for Stereotypic behaviours, indicating that the low verbal children tended to self-stimulate most when no demands were made on their behaviour. Implications for further research and educational practice are briefly discussed.

Attention↗

Response latency measurements to visual cognitive tasks by normal hearing and deaf subjects.

Visual cognitive differences between hearing (N = 16) and deaf (N = 32) high-school and middle-school students were studied. Visual tasks were presented on a microcomputer and response latencies were collected. Significant differences were noted between the deaf and normal groups but not between total communication deaf and oral deaf students. These differences support the hypothesis that deaf students prefer a visual cognitive strategy. Implications for educating the deaf are discussed.

Adolescent↗

Pilocarpine-induced purposeless chewing behaviour in rats is dependent on intact central stores of 5-HT.

Pilocarpine-induced purposeless chewing behaviour in rats was partially antagonised by pretreatment with reserpine, tetrabenazine or p-chlorophenylalanine (PCPA). In contrast, pretreatment with alpha-methyl-p-tyrosine (AMPT) had no effect on pilocarpine-induced chewing. These data suggest that enhancement of purposeless chewing by pilocarpine is dependent, in part, on intact central stores of 5-HT.

Animals↗

In vitro characterisation of dopamine receptors in the superior colliculus of the rat.

In membrane preparations of superior colliculus of the rat, the binding of [3H]spiperone (0.15 nM) was displaced by the incorporation of (+)-butaclamol, haloperidol, apomorphine and (+/-)-sulpiride, but not by (-)-butaclamol, prazosin, propranolol, ketanserin or cinanserin. The Ki values for the displacement of [3H]spiperone by (+/-)-sulpiride, (+)-butaclamol and haloperidol were similar in tissue preparations from superior colliculus and striatum. Equilibrium analysis of the specific binding of [3H]spiperone (0.03-1.0 nM), defined by 10(-5) M (+/-)-sulpiride, to membrane preparations of the superior colliculus, showed the interaction to be saturable and of high affinity. However, the Bmax was only approximately 10% of that found in preparations of striatum; the apparent dissociation constant (KD) was the same in both preparations of the superior colliculus and striatum. Uptake of [3H]dopamine into synaptosomal preparations of the superior colliculus was approximately 20% of that found in synaptosomes from the striatum. In preparations of striatum nomifensine, but not desipramine or fluoxetine, inhibited the uptake of [3H]dopamine. However, in preparations from the superior colliculus, nomifensine, desipramine and fluoxetine were without effect on the uptake of [3H]dopamine. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were present in small concentrations in the superior colliculus. Homovanillic acid (HVA) was present in larger concentrations and the HVA plus DOPAC/dopamine ratios were greater in the superior colliculus than in the striatum. The superior colliculus contained only small amounts of noradrenaline but 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were present in larger amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗