Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization
Dopamine receptors are classified into five subtypes, with D<sub>2</sub>R and D<sub>3</sub>R playing a crucial role in regulating mood, motivation, reward, and movement. Whereas D<sub>2</sub>R are distributed widely across the brain, including regions responsible...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6742 |
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| author | Kyeong-Man Kim |
| author_facet | Kyeong-Man Kim |
| author_sort | Kyeong-Man Kim |
| collection | DOAJ |
| description | Dopamine receptors are classified into five subtypes, with D<sub>2</sub>R and D<sub>3</sub>R playing a crucial role in regulating mood, motivation, reward, and movement. Whereas D<sub>2</sub>R are distributed widely across the brain, including regions responsible for motor functions, D<sub>3</sub>R 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, D<sub>2</sub>R and D<sub>3</sub>R have distinct regulatory properties involving desensitization, endocytosis, posttranslational modification, and interactions with other cellular components. In vivo, D<sub>3</sub>R is closely associated with behavioral sensitization, which leads to increased dopaminergic responses. Behavioral sensitization is believed to result from D<sub>3</sub>R desensitization, which removes the inhibitory effect of D<sub>3</sub>R on related behaviors. Whereas D<sub>2</sub>R maintains continuous signal transduction through agonist-induced receptor phosphorylation, arrestin recruitment, and endocytosis, which recycle and resensitize desensitized receptors, D<sub>3</sub>R rarely undergoes agonist-induced endocytosis and instead is desensitized after repeated agonist exposure. In addition, D<sub>3</sub>R 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 D<sub>3</sub>R could be linked to D<sub>3</sub>R-mediated behavioral sensitization. |
| first_indexed | 2024-03-11T05:33:40Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:33:40Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3fdf3624504b4b54a72d12079797f5692023-11-17T16:55:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01247674210.3390/ijms24076742Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral SensitizationKyeong-Man Kim0Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwang-Ju 61186, Republic of KoreaDopamine receptors are classified into five subtypes, with D<sub>2</sub>R and D<sub>3</sub>R playing a crucial role in regulating mood, motivation, reward, and movement. Whereas D<sub>2</sub>R are distributed widely across the brain, including regions responsible for motor functions, D<sub>3</sub>R 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, D<sub>2</sub>R and D<sub>3</sub>R have distinct regulatory properties involving desensitization, endocytosis, posttranslational modification, and interactions with other cellular components. In vivo, D<sub>3</sub>R is closely associated with behavioral sensitization, which leads to increased dopaminergic responses. Behavioral sensitization is believed to result from D<sub>3</sub>R desensitization, which removes the inhibitory effect of D<sub>3</sub>R on related behaviors. Whereas D<sub>2</sub>R maintains continuous signal transduction through agonist-induced receptor phosphorylation, arrestin recruitment, and endocytosis, which recycle and resensitize desensitized receptors, D<sub>3</sub>R rarely undergoes agonist-induced endocytosis and instead is desensitized after repeated agonist exposure. In addition, D<sub>3</sub>R 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 D<sub>3</sub>R could be linked to D<sub>3</sub>R-mediated behavioral sensitization.https://www.mdpi.com/1422-0067/24/7/6742dopamine D<sub>2</sub> and D<sub>3</sub> receptorsignal transductiondesensitizationintracellular traffickingbiased signalingposttranslational modification |
| spellingShingle | Kyeong-Man Kim Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization International Journal of Molecular Sciences dopamine D<sub>2</sub> and D<sub>3</sub> receptor signal transduction desensitization intracellular trafficking biased signaling posttranslational modification |
| title | Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization |
| title_full | Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization |
| title_fullStr | Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization |
| title_full_unstemmed | Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization |
| title_short | Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors and Their Impact on Behavioral Sensitization |
| title_sort | unveiling the differences in signaling and regulatory mechanisms between dopamine d sub 2 sub and d sub 3 sub receptors and their impact on behavioral sensitization |
| topic | dopamine D<sub>2</sub> and D<sub>3</sub> receptor signal transduction desensitization intracellular trafficking biased signaling posttranslational modification |
| url | https://www.mdpi.com/1422-0067/24/7/6742 |
| work_keys_str_mv | AT kyeongmankim unveilingthedifferencesinsignalingandregulatorymechanismsbetweendopaminedsub2subanddsub3subreceptorsandtheirimpactonbehavioralsensitization |