Low levels of mRNA for dopamine D4 receptor in human cerebral cortex and striatum.

Significant densities of mRNA for the dopamine D4 receptor in cerebral cortex, particularly in frontal lobe, have been reported in rats and monkeys, supporting the D4 hypothesis in the pathology of schizophrenia. Using northern blot analysis and the competitive reverse transcription-polymerase chain reaction (RT-PCR) method, we determined the relative levels of D4 mRNA in human brain regions to clarify whether the cortical level is also higher in humans. Northern blot analysis revealed an unexpected profile of D4 mRNA in the brain. The detected mRNA size, 1.5 kb, was quite different from the 5.3 kb reported in human neuroblastoma SK-N-MC cells. Higher levels of D4 mRNA were detected not only in the mesolimbic system but also in the corpus callosum, spinal cord, medulla, and subthalamic nucleus. It was surprising that in the cerebral cortex regions as well as the striatum, D4 mRNA was hardly detected. The competitive RT-PCR revealed these relative densities to be at least three orders of magnitude lower than that of the striatal D2 receptor. Our results demonstrate a remarkable difference in cortical D4 mRNA density in humans compared with that in rats and monkeys. Furthermore, the mRNA distribution suggests that the higher density of D4-like binding sites reported recently in normal human striatum is not due to the D4 receptor.