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Emerging roles of striatal dopamine D2 receptors in motivated behaviour: Implications for psychiatric disorders
Author(s) -
Olivetti Pedro R.,
Balsam Peter D.,
Simpson Eleanor H.,
Kellendonk Christoph
Publication year - 2020
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13271
Subject(s) - medium spiny neuron , neuroscience , dopamine , striatum , dopamine receptor d2 , psychology , schizophrenia (object oriented programming) , dopamine receptor , psychiatry
Impaired motivation has been a long recognized negative symptom of schizophrenia, as well as a common feature of non‐psychotic psychiatric disorders, responsible for a significant share of functional burden, and with limited treatment options. The striatum and dopamine signalling system play a central role in extracting motivationally relevant information from the environment, selecting which behavioural direction the animal should follow, and the vigour with which to engage it. Much of this function relies on striatal projection neurons, known as medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs), or D2‐MSNs. However, determining the precise nature of D2‐MSNs in regulating motivated behaviour in both healthy individuals and experimental manipulations of D2‐MSN function has at times yielded a somewhat confusing picture since their activity has been linked to either enhancement or dampening of motivation in animal models. In this MiniReview, we describe the latest data from rodent studies that investigated how D2Rs exert their modulatory effect on motivated behaviour by regulating striatal indirect pathway neuronal activity. We will include a discussion about how functional selectivity of D2Rs towards G protein–dependent or β‐arrestin–dependent signalling differentially affects motivated behaviour. Lastly, we will describe a recent preclinical attempt to improve motivation by exploiting serotonin receptor–mediated modulation of dopamine transmission in the striatum.