This video discusses the role of D2 and D3 receptors, 2 dopamine receptors that function as autoreceptors to help control dopamine release in the brain. They are believed to play an important role in mood regulation, particularly in patients with schizophrenia.
Transcript:
Understanding D2 and D3 receptors. There are 4 major dopamine pathways in the brain, and 5 major dopamine receptors subtypes. All receptor subtypes are found post-synaptically.
Only D2 and D3 receptors are also found pre-synaptically, where they function as autoreceptors to help regulate the synthesis and release of dopamine. When activated, autoreceptors inhibit dopamine release, and when antagonized, they allow dopamine release. D2 receptors are dispersed throughout the brain. Hyper-dopaminergic activity at some of these receptors are thought to be associated with positive symptoms of schizophrenia. Conversely, under-activation of certain D2 receptors due to either reduced endogenous dopamine or significant antagonism are thought to be associated with negative symptoms of schizophrenia and may be associated with hyperprolactinemia and extrapyramidal symptoms. D3 receptors are less abundant than D2 receptors and are mainly expressed in limbic areas.
Dopamine's affinity for the D3 receptor is greater than for the D2 receptor. In vivo studies have shown that post-synaptic D3 receptors are expressed in specific limbic regions, such as the nucleus accumbens. Antagonism or partial agonism of D3 receptors here may have antipsychotic effects. Animal model studies suggest that D3 receptor antagonism could also theoretically improve mood.
Dopamine neurons projecting from the ventral tegmentum to the prefrontal cortex can have D3 autoreceptors located on their neuronal cell body. Here, antagonism or partial agonism may increase dopamine release in the prefrontal cortex, and it is hypothesized that this may help improve mood and negative symptoms of schizophrenia.
D2 and D3 are unique among the dopamine receptor subtypes and are thought to play an important role in mood regulation.
References
Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013.
Stahl SM. Dazzled by the dominions of dopamine: clinical roles of D3, D2, and D1 receptors. CNS Spectr. 2017;22(4):305-311. doi:10.1017/S1092852917000426
Gross G, Drescher K. The role of dopamine D(3) receptors in antipsychotic activity and cognitive functions. Handb Exp Pharmacol. 2012:(213):167-210. doi:10.1007/978-3-642-25758-2_7
Brichta L, Greengard P, Flajolet M. Advances in the pharmacological treatment of Parkinson's disease: targeting neurotransmitter systems. Trends Neurosci. 2013;36(9):543-554. doi:10.1016/j.tins.2013.06.003
Brunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw Hill; 2011.
Leggio GM, Bucolo C, Platania CBM, Salomone S, Drago F. Current drug treatments targeting dopamine D3 receptor. Pharmacol Ther. 2016:165:164-177. doi: 10.1016/j.pharmthera.2016.06.007
Murray AM, Ryoo HL, Gurevich E, Joyce JN. Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain. Proc Natl Acad Sci USA. 1994;91(23):11271-11275. doi:10.1073/pnas.91.23.11271
Diaz J, Pilon C, Le Foll B, et al. Dopamine D3 receptors expressed by all mesencephalic dopamine neurons. J Neurosci. 2000;20(23):8677-8684. doi:10.1523/JNEUROSCI.20-23-08677.2000
Sokoloff P, Andrieux M, Besançon R, et al. Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor. Eur J Pharmacol. 1992;225(4):331-337. doi:10.1016/0922-4106(92)90107-7
Sokoloff P, Le Foll B. The dopamine D3 receptor, a quarter century later. Eur J Neurosci. 2017;45(1):2-19. doi:10.1111/ejn.13390
Torrisi SA, Geraci F, Contarini G, Salomone S, Drago F, Leggio GM. Dopamine D3 receptor, cognition and cognitive dysfunctions in neuropsychiatric disorders: from the bench to the bedside. Curr Top Behav Neurosci. 2023:60:133-156. doi:10.1007/7854_2022_326
Stahl SM. Drugs for psychosis and mood: unique actions at D3, D2, and D1 dopamine receptor subtypes. CNS Spectrums. 2017;22(5):375-384. doi:10.1017/S1092852917000608
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