Multiple dopamine receptors and behavior

Abstract

The therapeutic effects of dopamine (DA) agonists and DA antagonists used in the treatment of schizophrenia (antipsychotics, DA antagonists), Huntington's chorea (DA antagonists) and Parkinson's disease (antiparkinsonian agents, DA agonists) have been thought to result largely from actions on DA receptors located in the striatum (caudate nucleus and putamen). Many of the classical drugs used to treat these disorders are known to have a high incidence of extrapyramidal side effects (EPS). However, a number of drugs, the atypical antipsychotics and antiparkinsonian agents, have been developed which have a low incidence of EPS. It has been of enormous interest to researchers and clinicians alike to determine what characteristics of the atypical antipsychotics and antiparkinsonian agents are responsible for their unique behavioral profile. Because all of the antipsychotics and antiparkinsonian agents act on DA receptors, much attention has focused on potential differences in the interactions of the atypical agents with DA receptors. An hypothesis that has been raised, due to the knowledge that there are multiple subtypes of DA receptors located in the striatum, is that the atypical agents could have their therapeutic actions as a result of an interaction with one specific subtype of DA receptor. This review emphasizes two major points: (1) it is unlikely that the atypical antipsychotics and antiparkinsonian agents interact with only one subtype of DA receptor, or have their therapeutic actions only through that receptor; (2) other pharmacological characteristics of these agents are more critically involved in their unique behavioral effects. The applicability of animal models to assess the pharmacological and behavioral profiles of these agents is discussed, and the relevance to the clinical profiles of these agents is emphasized.