Interactions between D1 and D2 Dopamine Receptor Mechanisms: The Immediate Early Response Gene C-Fos in Long-Term Changes in the Striatum

Abstract

As recently as 1984, it was possible to refer to the D2 dopamine site as the only functional, behaviourally relevant dopamine receptor; the significance of the D1 site, beyond adenylate cyclase stimulation, was unknown (Grigoriadis and Seeman, 1984). It is now clear that Dl and D2 dopamine receptor mechanisms interact in such a way as to produce additive or synergistic effects on many behavioural and movement-related functions in rats, mice, monkeys and, most likely, in man. The exact mechanisms by which this occurs remains obscure. Here we review the evidence for additive or synergistic effects of D1 and D2 receptor mechanisms and discuss the anatomical implications of these findings. Interaction between D1 and D2 dopamine receptor mechanism may also have important long-term consequences. These long-term consequences include important clinical phenomena such as the tardive dyskinesias and dystonias. In addition to these movement disorders, there is at least reason to suspect that these mechanisms (D1/D2 receptor mechanism interaction, immediate early gene activation) might be involved in major psychiatric illnesses such as the schizophrenias. In animal studies, the phenomenon of dopaminergic “priming” may be a model for the sorts of long-term changes that occur clinically in these psychiatric illnesses and motor disturbances.