Receptor–receptor interactions within receptor mosaics. Impact on neuropsychopharmacology

摘要: Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing mosaics (RM; dimeric high-order oligomers) where it is believed that D-2 operate as 'hub receptor' these complexes. The constitutive adenosine A(2A)/dopamine RM, located in dorsal striatopallidal GABA neurons, are particular interest view demonstrated antagonistic A(2A)/D-2 interaction heteromers; an led to suggestion later demonstration A(2A) antagonists could be used novel anti-Parkinsonian drugs. Based likely A(2A)/D-2/mGluR5 RM both extrasynaptically striato-pallidal neurons cortico-striatal glutamate terminals, multiple this involving synergism between A(2A)/mGluR5 counteract has proposal using combined mGluR5 a future treatment. same ventral pathways, strategies treatment schizophrenia, building idea agonists and/or will help reduce increased signaling have been suggested. Such ensure proper glutamatergic drive from mediodorsal thalamic nucleus prefrontal cortex, one which reduced due dominance D-2-like striatum. Recently, receptors also shown locomotor sensitizing actions cocaine increases observed accumbens after extended self-administration, probably representing compensatory up-regulation cocaine-induced D-3 signaling. Therefore, agonists, through antagonizing A(2)/D-3 heteromers accumbens, found useful dependence. Furthermore, cannabinoid CB1/D-2 requiring discovered possibly CB1/D-2/A(2A) principally striatal terminals but some thereby opening up new mechanism integration endocannabinoid, DA mediated signals. Thus, A(2A), CB1 can form integrative units displaying different compositions, topography localization. Also galaninR/5-HT1A participates transmission ascending 5-hydroxytryptamine galanin antagonize 5-HT1A recognition Subtype specific therefore represent antidepressant These results suggest importance complete understanding function regard disease. Ultimately receptor-recepor modify serotonergic give wide range