Reserpine rigidity and adrenergic neurones.
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Biomedical subjects
Publications and source records attributed to R A Webster.
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1. Spontaneous exploratory locomotor activity of Wistar rats was measured in photocell activity cages, and brain noradrenaline (NA) and dopamine (DA) were determined fluorometrically after ion exchange purification.2. Tetrabenazine (TBZ) (10 mg/kg) produced a fall in NA and DA concentrations in rat brain stems which was correlated with the fall in activity in female Wistar rats.3. alpha-Methyl-m-tyrosine (alphaMMT) reduced the concentration of rat brain NA without affecting DA concentration or activity.4. Pretreatment with alphaMMT did not stop TBZ from producing a marked reduction in activity and NA concentration, but partially protected DA from the depleting action of TBZ.5. These results support a role for catecholamines in the control of motor activity, but they do not implicate NA more than DA and they emphasize that the mechanism by which drugs affect the concentrations of catecholamines may be more important than the gross concentrations attained.
1. Spontaneous locomotor activity (activity) in male Wistar rats was compared with the concentrations of brain noradrenaline (NA), dopamine (DA) and metaraminol.2. alpha-Methyl-m-tyrosine (alphaMMT) (400 mg/kg) reduced the concentrations of DA as well as NA but activity remained high in the presence of metaraminol formed from the alphaMMT. When tetrabenazine (TBZ) was given after alphaMMT pretreatment there was a fall in the levels of activity and in the concentrations of NA, DA and metaraminol.3. alpha-Methyl-p-tyrosine (alphaMT) produced a fall in activity which was correlated with falls in the concentrations of NA and DA. 5-Hydroxytryptamine (5-HT) did not appear to be affected.4. After depletion of NA and DA by alphaMT and TBZ, administration of L-dopa produced a return in activity which was significantly correlated with the concentration of NA but not DA. When alphaMMT was given to a similar group of pretreated animals there was no recovery of activity despite high concentrations of DA and metaraminol.5. The dopamine beta hydroxylase inhibitor, diethyldithiocarbamate (DDC), suppressed activity as well as the concentrations of NA and DA at high doses (750 mg/kg) but smaller doses (400 mg/kg) plus L-dopa gave high DA concentrations without activity.6. It is concluded that NA and not DA is associated with activity but that it is only part of the total NA which is in the biosynthetic storage granule affected by drugs like alphaMT and TBZ, which controls activity. Drugs that do not affect this pool may lower NA concentrations but not reduce activity.7. The replacement of NA by metaraminol in this functional pool does not restore activity.
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1. Acute administration of tetrabenazine produced tremor in cats, in doses which caused sedation but not hypothermia.2. The pattern of movements resembled shivering rather than Parkinsonism, and warming the skin suppressed the tremor.3. The tremor was not influenced by hyoscine.4. Tremor produced by amylobarbitone was essentially similar to that induced by tetrabenazine.
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