Direct and indirect interactions of the dopamine D₃ receptor with glutamate pathways: implications for the treatment of schizophrenia

Naunyn-Schmiedeberg's Archives of Pharmacology
Pierre SokoloffRené Pumain

Abstract

This article, based on original data as well as on previously reported preclinical and clinical data that are reviewed, describes direct and indirect interactions of the D(3) receptor with N-methyl-D-aspartate receptor (NMDA) signaling and their functional consequences and therapeutic implications for schizophrenia. D(3) receptor immunoreactivity at ultrastructural level with electron microscopy was identified at presumably glutamatergic, asymmetric synapses of the medium-sized spiny neurons of the nucleus accumbens. This finding supports the existence of a direct interaction of the D(3) receptor with glutamate, in line with previously described interactions with NMDA signaling involving Ca(2+)/calmodulin-dependent protein kinase II at post-synaptic densities (Liu et al. 2009). Indirect interactions of the D(3) receptor with glutamate could involve a negative control exerted by the D(3) receptor on mesocortical dopamine neurons and the complex regulation of the glutamatergic pyramidal cells by dopamine in the prefrontal cortex. This could be exemplified here by the regulation of pyramidal cell activity in conditions of chronic NMDA receptor blockade with dizocilpine (MK-801). BP897, a D(3) receptor-selective partial agonist, re...Continue Reading

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Related Concepts

Antipsychotic Effect
Biochemical Pathway
Behavior, Animal
Exertion
Immunoreactivity
Prefrontal Cortex
Dopamine D3 receptor
Schizophrenia
Piperazines
Neurons

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