Transcription Mechanisms for Dopamine Receptor Genes

Transcription regulation is a complex but key control mechanism that underlies differential gene expression during development and in the adult organism. Like all protein coding genes, those encoding dopamine receptors are subject to this form of regulation as well. Modifications in dopamine receptors have been implicated in a number of neurobehavioral disorders, including Parkinson’s disease and schizophrenia, as well as in the complications of their long-term therapy (1 –5 ). Based on clinical pharmacologic observations in parkinsonian and schizophrenic patients, the D₂ dopamine receptor has traditionally been thought to be the main mediator of the motor and behavioral effects of dopamine (1 ,6 ). More recent molecular and neurophysiologic advances, in addition to the availability of receptor-selective pharmacologic agents, have clarified the importance of the D₁ class of dopamine receptors as well (7 ,8 ). The D_1A dopamine receptor is one of two dopamine receptors abundantly expressed in the striatum (9 ), suggesting that it has a critical role in transmitting the nigrostriatal dopaminergic signal resulting in normal motor function. In the prefrontal cortex, the D_1A receptor is more abundantly expressed than the D₂ receptor (10 ) and has been shown to modulate memory (11 ).