Insights into the Role of Dopamine Receptor Systems in Learning and Memory

Abstract

It is well established that learning and memory are complex processes involving and recruiting different brain modulatory neurotransmitter systems. Considerable evidence points to the involvement of dopamine in various aspects of cognition, and interest has been focused on investigating the clinical relevance of dopamine systems to age-related cognitive decline and manifestations of cognitive impairment in schizophrenia, Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. In the past decade or so, in spite of the molecular cloning of the five dopamine receptor subtypes, their specific roles in brain function remained inconclusive due to the lack of completely selective ligands that could distinguish between the members of the D1-like and D2-like dopamine receptor families. One of the most important advances in the field of dopamine research has been the generation of mutant mouse models permitting evaluation of the dopaminergic system using gene targeting technologies. These mouse models represent an important approach to explore the functional roles of closely related receptor subtypes. In this review, we present and discuss evidence on the role of dopamine receptors in different aspects of learning and memory at the cellular, molecular and behavioral levels. We compare evidence using conventional pharmacological, lesion or electrophysiological studies with results from mice with targeted deletions of different subtypes of dopamine receptor genes. We particularly focus on dopamine D1 and D2 receptors in an effort to delineate their specific roles in various aspects of cognitive function. We provide strong evidence, from our own recent work as well as others, that dopamine is part of the network that plays a very important role in cognitive function, and that although multiple dopamine receptor subtypes contribute to different aspects of learning and memory, the D1 receptor seems to play a more prominent role in mediating plasticity and specific aspects of cognitive function, including spatial learning and memory processes, reversal learning, extinction learning, and incentive learning.