The distributions of the transcripts encoding the five dopamine receptors have been determined in the human striatum and selected regions of the neocortex. In the striatum significant levels of dopamine receptor expression are restricted to the D1, D2, and D3 receptors. D1 and D2 receptor messenger ribonucleic acids (mRNAs) are homogeneously distributed throughout the caudate, putamen, and nucleus accumbens. D3 receptor mRNA is particularly enriched in the nucleus accumbens, with moderate levels in the ventral putamen. In the prefrontal cortex D1 and D4 receptor mRNAs are the most abundant, although the other three transcripts are seen at lower levels. A similar pattern is seen in the temporal neocortex. In the occipital cortex, D1 receptor mRNA is the most abundant, D3 the rarest, while the other three transcripts are present at modest levels of expression. These data add to a growing understanding of the neuroanatomical distribution of these transcripts in the human brain. They are essential to understand in the context of the limbic circuitry of the brain, as new hypotheses of dysfunction of dopaminergic neurotransmission are advanced in psychiatry and as these receptor subtypes are targeted for development of novel pharmacological treatments.

The distribution of the messenger RNA encoding the dopamine D5 receptor was determined in the rat brain by in situ hybridization. Using [35S]-labelled riboprobes to either the rat or human D5 receptor, this mRNA was localized to the hippocampus and the parafascicular nucleus of the thalamus. This mRNA could not be visualized in the more traditional brain regions associated with dopaminergic cell bodies or projection fields. This unusual distribution suggests a novel function in the brain for this subtype of the dopamine receptor.

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The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human.

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