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Chapter 4 Dopamine receptors

Elsevier Ltd
DOI: 10.1016/s1569-2582(97)80066-9
  • Biology
  • Chemistry
  • Medicine
  • Pharmacology


Summary This chapter provides an overview of recent developments in dopamine receptor biochemistry with emphasis on its relation to psychiatric and neurological diseases. Dopamine receptors control pathways involved in movement, due to their strategic location in the basal ganglia. Several elegant behavioral tests have been developed based on the findings that locomotor activity is strongly affected by dopamine receptor antagonists. Dopamine antagonists (antischizophrenic drugs) also affect cognitive, motivational, and emotional processes, primarily due to the location of dopamine receptors in the limbic system. Molecular cloning techniques revealed the presence of at least five dopamine receptor subtypes in the brain that can be grouped in two families; the D1 receptor family which stimulates cAMP formation, and the D2 receptor family which exerts an inhibitory effect on cAMP synthesis. Receptor binding studies revealed that both the D1 and the D2 receptor families are coupled to G proteins. However, differences in structure, molecular weights, anatomical distribution, biochemical characteristics, and pharmacological profiles between the different receptor subtypes have been reported. Dopamine receptors have been implicated in a variety of neurological disorders, mainly in Parkinson's disease and schizophrenia. Parkinson's disease is characterized by a severe loss in striatal dopamine. The symptoms of the disease can be reversed by L-Dopa, the precursor amino acid of dopamine. Prolonged treatment with L-Dopa, however, often leads to dyskinesias and to a variety of psychiatric complications. As for the schizophrenia, one plausible explanation in its development involves a deficit in the mesolimbic pathway, leading to a hyperactivity of the dopamine neurons. Chronic treatment with typical antipsychotics appears to be beneficial but often leads to a serious movement disorder called tardive dyskinesia. Therefore, continual efforts are needed in order to obtain a better understanding of the etiology and hence the treatment of Parkinson's disease and schizophrenia.

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