A Historical Perspective on the Dopamine D3 Receptor

Sokoloff, Pierre; Foll, Bernard Le

doi:10.1007/7854_2022_315

Cited by 1 publication

(2 citation statements)

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“…Establishing a correlation between the in vivo roles of certain GPCRs and their biochemical characteristics in vitro is challenging. Both D 2 R and D 3 R are involved in regulating locomotion, reward, and addiction, but D 3 Rs appear to have a more specific role in regulating emotional and cognitive processes that involve behavioral sensitization [ 37 ]. Evidence suggests that behavioral sensitization is closely related to the plasticity of limbic neurochemical systems [ 193 , 194 ], which are also implicated in a range of psychiatric and substance use disorders.…”

Section: Discussionmentioning

confidence: 99%

“…The main objective of this review is to comprehend the functional implications of the distinct regulatory processes of D 2 R and D 3 R by highlighting their differences. Functional in vivo roles and ligands of D 2 R and D 3 R are described in other excellent reviews [ 33 , 34 , 35 , 36 , 37 ]. This review focuses on the regulatory functions of D 2 R and D 3 R in biochemical pathways.…”

Section: Introductionmentioning

confidence: 99%

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Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D2 and D3 Receptors and Their Impact on Behavioral Sensitization

Kim

2023

IJMS

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Dopamine receptors are classified into five subtypes, with D2R and D3R playing a crucial role in regulating mood, motivation, reward, and movement. Whereas D2R are distributed widely across the brain, including regions responsible for motor functions, D3R are primarily found in specific areas related to cognitive and emotional functions, such as the nucleus accumbens, limbic system, and prefrontal cortex. Despite their high sequence homology and similar signaling pathways, D2R and D3R have distinct regulatory properties involving desensitization, endocytosis, posttranslational modification, and interactions with other cellular components. In vivo, D3R is closely associated with behavioral sensitization, which leads to increased dopaminergic responses. Behavioral sensitization is believed to result from D3R desensitization, which removes the inhibitory effect of D3R on related behaviors. Whereas D2R maintains continuous signal transduction through agonist-induced receptor phosphorylation, arrestin recruitment, and endocytosis, which recycle and resensitize desensitized receptors, D3R rarely undergoes agonist-induced endocytosis and instead is desensitized after repeated agonist exposure. In addition, D3R undergoes more extensive posttranslational modifications, such as glycosylation and palmitoylation, which are needed for its desensitization. Overall, a series of biochemical settings more closely related to D3R could be linked to D3R-mediated behavioral sensitization.

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Section: Discussionmentioning

confidence: 99%