Parkinson’s disease (PD) and L-DOPA-induced dyskinesia, a major complication of treatment of PD, are
associated with molecular and functional alterations occurring into the medium spiny neurons (MSNs) of the dorsal
striatum, a key areas involved in the control of motor activity. MSNs are regulated by several neurotransmitter systems
including dopamine, glutamate and adenosine via activation of distinct receptors. Increasing evidence suggest that
interactions among systems are mediated by different mechanisms including the formation of receptor heterodimers. The
current view of G protein-coupled receptors organization, in fact, assumes that they do not work as monomeric units, but
are part of heterodimeric complexes or of high order heteromers, where other receptors and ancillary proteins are coclustered.
This organization implies that the pharmacological and signalling properties of these receptors may depend on
the molecular composition of the receptor heteromers where they are clustered and may be differentially modulated in
physiological or pathological conditions.
Here, we provide an overview of the functional implications of physical interactions among dopamine, glutamate and
adenosine receptors, their relevance for striatal MSNs activity and their involvement in the physiopathology of PD and