Layer V neurons bear the majority of mRNAs encoding the five distinct dopamine receptor subtypes in the primate prefrontal cortex.

In situ hybridization histochemistry was used to determine the laminar distribution of D1, D2, D3, D4, and D5 dopamine receptor mRNAs in the primate prefrontal cortex and to compare striatal and cortical levels of these messages within the same tissue sections. All five subtypes of dopamine receptor mRNA are present in both the monkey striatum and the cerebral cortex but in different proportions within each structure. Thus, levels of D1 and D2 mRNAs are noticeably stronger in the striatum than in the cortex, whereas D4 and D5 expression is clearly higher in the cortex. The D3 transcripts appear nearly equivalent in the striatum and the cortex. A major finding is that, within the prefrontal cortex, mRNAs encoding all dopamine receptor subtypes are expressed most strongly in layer V. This laminar pattern of mRNA distribution does not hold in all cortical regions. The relatively high levels of mRNAs encoding known dopamine receptor subtypes in the primate cerebral cortex, including the D4 receptor, underscore the importance of this structure as a target for therapeutic actions of antipsychotic drugs. Further, their prominence in layer V of the prefrontal cortex, which contains the corticostriatal and corticotectal projection neurons, provides a neural basis for dopaminergic regulation of the descending control systems.