Interactions between NMDA and dopamine receptors: A potential therapeutic target

Many pathological processes are associated with a malfunction of one or multiple postsynaptic neurotransmitter receptors. It would seem that simple agonists or antagonists at these receptors should be able to correct the pathological condition. However, these drugs often fail due to serious side effects that are caused by suppressing post-synaptic responses necessary for normal brain function. Thus, there is a need for new drugs that can selectively target specific post-synaptic pathways. The dopamine and glutamate receptor systems have been implicated in many neuropsychiatric disorders. Dopamine, the predominant catecholamine in the mammalian brain, influences a variety of functions including locomotor activity, cognition, emotion and endocrine regulation. Glutamate is the principal excitatory neurotransmitter, involved in regulating neuronal circuit development, learning and memory. The overlap and convergence of both dopaminergic and glutamatergic projections in the brain provides a framework for complex neuronal interactions between these receptor systems. In this review, we will focus on interactions between the NMDA glutamate receptor and dopamine D1 and D2 receptors, and address the potential value of receptor heteromers in seeking novel therapeutic targets. This article is part of a Special Issue entitled: Brain Integration. (C) 2012 Elsevier B.V. All rights reserved.