The role of the dopaminergic nigrostriatal system in controlling the excitability of neostriatal neurons has been intensely studied, since it became clear that the loss of this innervation was responsible for the psycho-motor symptoms of Parkinson's disease. In past years, the actions of dopamine have been attributed to activation of two types of dopamine receptor. The application of molecular cloning techniques in characterizing these receptors has revealed that rather than two there are at least six dopamine receptors (D1, D2S, D21, D3, D4, and D5). All share a similar structural motif that is characteristic of G protein-coupled catecholamine receptors. In situ hybridization and Northern blot analyses suggest that all six receptors are expressed in the neostriatum with the D1 and D2 subtypes being the predominant forms in the dorsal striatum. The existence of so many receptors has made understanding actions of dopamine an even more daunting task than previously imagined, especially in the light of ones growing awareness of the biochemical heterogeneity of medium spiny neurons. Faced with this sort of complexity, simplifying hypotheses become particularly appealing. One such hypothesis that appears to make dopamine's actions in the striatum more tractable is that, dopamine receptor subtypes are segregated in striatal projection neurons. There are two lines of study that support this hypothesis. First, Gerfen et al.'s work has shown that in 6-hydroxydopamine-lesioned or haloperidol-treated striatum, D2-class agonists can selectively alter the levels of enkephalin mRNA in striatopallidal neurons, whereas D1-class agonists selectively alter the levels of substance P in striatonigral neurons. Second, both Gerfen and Le Moine et al., have reported that D1 and D2 receptor mRNAs are found only in striatonigral and striatopallidal neurons, respectively.
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