The importance of the nigrostriatal dopaminergic pathway in motor control is widely accepted and it is generally believed that the motor symptoms of Parkinson's disease result solely from reduced release of dopamine from terminals in the striatum. Over recent years there has been a growing body of evidence which suggests that dendritic dopamine release in the substantia nigra is of importance in the regulation of neuronal activity and behaviour. This evidence is reviewed together with a description of our recent findings that show nigral dopamine receptors are essential for the maintenance of normal muscle tone. It is concluded that current views of the basal ganglia circuitry involved in motor control need to be re-evaluated to take into account these recent reports. A scheme is suggested to explain how dopamine mechanisms in the substantia nigra regulate motor activity.

Summary and conclusionsEighteen hot flushes experienced by eight menopausal women were studied and compared with the effects of warming in six premenopausal women. The hot flushes were associated with an acute rise in skin temperature, peripheral vasodilatation, a transient increase in heart rate, fluctuations in the electrocardiographic (ECG) baseline, and a pronounced decrease in skin resistance. Although premenopausal women had greater maximum increases in skin temperature and peripheral vasodilatation, they showed a much smaller decrease in skin resistance and no changes in heart rate or ECG baseline.These findings suggest that the onset of the hot flush is associated with a sudden and transient increase in sympathetic drive. Further investigations may lead to the development of a more specific alternative to oestrogen for relieving menopausal hot flushes.

The aim of the present study was to localize the dopamine receptors involved in the regulation of muscle tone. A strategy was used whereby the effects on muscle tone of injecting the irreversible dopamine receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in discrete brain regions were assessed. Increases in muscle tone were measured as changes in electromyographic activity of the gastrocnemius and tibialis muscles of conscious, unrestrained rats. No increases in muscle tone were found after injections of EEDQ into the anterior and posterior striatum, which produced marked reductions in dopamine receptor concentration. The effects on muscle tone of injecting EEDQ into the substantia nigra pars reticulata were also assessed. Large increases in muscle tone were observed associated with inactivation of either D1 or D2 dopamine receptors in the substantia nigra. The increased muscle tone was not reduced by subcutaneous administration of apomorphine, despite the presence of a normal population of striatal dopamine receptors. These findings provide evidence that dopamine receptors in the substantia nigra play an important role in the regulation of muscle tone. Further, they challenge the hypothesis that the muscle rigidity of Parkinson disease results primarily from loss of striatal dopamine receptor stimulation.The association of the characteristic symptoms of Parkinson disease-bradykinesia, tremor, and rigidity-with degeneration of nigrostriatal neurons (1) has led to the hypothesis that the neurochemical mechanism underlying these symptoms is a loss of dopamine release in the striatum. The success of L-dihydroxyphenylalanine (L-dopa) in alleviating the motor symptoms of Parkinson disease is attributed to augmentation of dopamine stores and the maintenance of striatal dopamine receptor stimulation (2). Experimental findings have also shown increased muscle tone (muscle rigidity) associated with reductions in striatal dopamine after lesioning of nigrostriatal neurons by the neurotoxin 6-hydroxydopamine (3) or after treatment with reserpine (3, 4).Although these findings have been interpreted as support for the striatal dopamine hypothesis, they have not taken into account that nigral dopaminergic neurons release dopamine from both their dendrites (5) and their terminals, so that dopamine concentration in the substantia nigra, as well as the striatum, will be reduced in Parkinson disease and after reserpine or 6-hydroxydopamine treatment. The aim of the present study was to investigate the role of striatal and nigral dopamine receptors in the regulation of muscle tone. The irreversible dopamine receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was injected into these regions, and the effects on muscle tone, measured as changes in the electromyographic (EMG) activity of the antagonistic muscles of the hind limb, were recorded. The area and extent of the resulting dopamine receptor inactivation were assessed using quantitative autoradiography so that the The publica...

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