Characterization of brain dopaminergic receptors in Huntington's disease.
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Central dopaminergic neurons play an important role in motor, emotional, and cog nitive behavior. These dopaminergic systems are affected both by normal aging and by various diseases. The most prominent of these diseases is Parkinson's disease, which is associated with a gradual and progressive loss of dopaminergic neurons in the human brain. Studies on human brain have revealed a remarkable ability of these neurons to compensate for partial destruction of their systems, and these findings have prompted numerous investigations of the adaptive changes of dopaminergic neurons to experimental injury. The findings reveal that dopaminergic neurons react to a partial lesion of their pathways with several adaptive changes. Dopaminergic neurons surviving a partial lesion respond by increasing transmitter synthesis and release. Furthermore, after near-total lesions, a supersensitivity of postsynaptic transmitter receptors develops. Because of these bio chemical adaptive changes, few surviving neurons are able to compensate for the loss of a majority of other dopaminergic neurons. Recent findings indicate that biochemical adaptive processes can be further stimulated by pharmacological manipulation. The possible mechanisms of actions of these pharmacological agents are discussed.
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Brainstem monoamine areas such as the ventral tegmental area (VTA) send dopaminergic projections to the cerebral cortex that are widely distributed across different cortical regions. Whereas the projection to prefrontal areas (PFC) has been studied in detail, little is known about dopaminergic projections to primary motor cortex (M1). These projections have been anatomically characterized in rat and primate M1. Primates have even denser dopaminergic projections to M1 than rats. The physiological role, the effects of dopaminergic input on the activity of M1 circuits, and the behavioral function of this projection are unknown. This review explores the existing anatomical, electrophysiological and behavioral evidence on dopaminergic projections to M1 and speculates about its functional role. The projection may explain basic features of motor learning and memory phenomena. It is of clinical interest because of its potential for augmenting motor recovery after a brain lesion as well as for understanding the symptomatology of patients with Parkinson's disease. Therefore, targeted investigations are necessary.
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