Conventional and Novel Pharmacological Approaches to Treat Dopamine-Related Disorders: Focus on Parkinson's Disease and Schizophrenia

Abstract

The dopaminergic system integrated by cell groups distributed in several brain regions exerts a modulatory role in brain. Particularly important for this task are the mesencephalic dopamine neurons, which from the substantia nigra and ventral tegmental area project to the dorsal striatum and the cortical/subcortical limbic systems, respectively. Dopamine released from these neurons operates mainly via the short distance extrasynaptic volume transmission and activates five different dopaminergic receptor subtypes modulating synaptic GABA and glutamate transmission. To accomplish this task dopaminergic neurons keep mutual modulating interactions with neurons of other neurotransmitter systems, including allosteric receptor-receptor interactions in heteroreceptor complexes. As a result of its modulatory role dopaminergic mechanisms are involved in either the etiology or physiopathology of many brain diseases such as Parkinsońs disease and schizophrenia. The aim of this work is to review some novel and conventional approaches that either have been used or are currently employed to treat these diseases. Particular attention is paid to the approaches derived from the knowledge recently acquired in the realm of receptor-receptor interactions taking place through multiple dopamine heteroreceptor complexes in the plasma membrane. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.

Keywords: Parkinson’s disease; dopamine; heteromer complexes; receptor oligomerization.