[Brain dopamine receptors: molecular aspects and functional implications]

During the last decade, molecular biology methods have primarily contributed to the fine characterisation of five subtypes of dopaminergic receptors leading to the classification of the D1-like (D1 and D5) and D2-like (D2, D3 and D4) subclasses. Biochemical methods have provided evidences for a large diversity of transduction mechanisms associated to these different receptors which can contribute to explain the multiple actions of dopamine at cellular level in the brain, from changes in membrane excitability to influences of gene expression. Moreover, the characteristic intracerebral distribution of these receptors subtypes supports the involvement of the neurotransmitter in different aspects of behaviour, from motor to limbic and cognitive aspects. In this respect, in Parkinson's disease dopamine depletion will favour adaptive responses at the cellular level which likely involve differentially the dopaminergic receptor subtypes. Such adaptive responses involving long-lasting processes of intercellular communication will either act to limit the symptoms of the disease or, more likely, to contribute to the expression of clinical signs. The development of appropriate agonists to selectively stimulate the different subsets of receptors still remains a challenge but, actually, already contributes to efficiently compensate for the motor signs of Parkinson's disease. In any case, such dopaminergic agonists are considered as an essential strategy to limit the motor side effects of L-DOPAtherapy. Thus, the development of more selective agonists of the different subsets of the dopamine receptors may contribute to compensate for the other clinical signs of the disease, and particularly for cognitive deficits.