{"id":1,"date":"2022-08-25T08:00:22","date_gmt":"2022-08-25T08:00:22","guid":{"rendered":"http:\/\/lifeandmindart.com\/?p=1"},"modified":"2022-08-25T11:34:32","modified_gmt":"2022-08-25T11:34:32","slug":"hello-world","status":"publish","type":"post","link":"https:\/\/lifeandmindart.com\/en\/2022\/08\/25\/hello-world\/","title":{"rendered":"ROLUL DOPAMINEI \u00ceN CREIER \u0218I S\u0102N\u0102TATE"},"content":{"rendered":"

Citation: <\/strong>Ceciu, Ramona L. 2022. Rolul Dopaminei \u00een Creier \u0219i S\u0103n\u0103tate. Life and Mind Art Research <\/em>journal, no. 2, August. Paper initially presented at the University of Bucharest on 8 Jan. 2022. (Please include the link when you cite this article and add the access date).<\/p>\n\n\n\n

Introducere<\/strong><\/p>\n\n\n\n

Dopamina este unul dintre cei mai cunoscu\u021bi neurotransmi\u021b\u0103tori, al\u0103turi de serotonin\u0103, acetilcolin\u0103, GABA (acidul gamaaminobutiric) \u0219i mul\u021bi al\u021bi neurotransmi\u021b\u0103tori juc\u00e2nd rol major \u00een s\u0103n\u0103tatea noastr\u0103 fizic\u0103 \u0219i psihic\u0103. Nivelul de dopamin\u0103 este asociat cu nivelul de energie, starea psiho-emo\u021bional\u0103, motiva\u021bia unei peroane de a se angaja \u00een diverse ac\u021biuni \u0219i activit\u0103\u021bi recompensatorii, comportamente legate de alimenta\u021bie, sex \u0219i adic\u021bii, un nivel sc\u0103zut de dopamin\u0103 implic\u00e2nd apari\u021bia unor tendin\u021be spre consum de alcool \u0219i alte substan\u021be stimulante, spre consum de dulciuri \u0219i carbohidra\u021bi care adesea duce la supraponderalitate.<\/p>\n\n\n\n

Sintez\u0103, mecanisme de ac\u021biune, circuit dopaminergic \u2013 studii<\/strong><\/p>\n\n\n\n

Dopamina face parte din clasa aminelor biogene, fiind o catecolamin\u0103 natural\u0103, derivat\u0103 din tirozin\u0103 \u0219i precursoare a norepinefrinei \u0219i epinefrinei. Dopamina este neurotransmi\u021b\u0103tor \u00een anumite zone ale sistemului nervos central, \u00een special \u00een tractul nigrostriatal \u0219i \u00een c\u00e2\u021biva nervi simpatici periferici. Ca mecanism de ac\u021biune, dopamina produce efecte cronotrope \u0219i inotrope pozitive asupra miocardului, duc\u00e2nd la cre\u0219terea frecven\u021bei cardiace \u0219i a contractilit\u0103\u021bii cardiace (cf. DrugBank<\/em>). Acest lucru se realizeaz\u0103 direct prin exercitarea unei ac\u021biuni agoniste asupra receptorilor beta-adrenergici \u0219i indirect prin determinarea eliber\u0103rii norepinefrinei din locurile de stocare \u00een termina\u021biile nervoase simpatice. \u00cen creier dopamina ac\u021bioneaz\u0103 ca un agonist al celor cinci subtipuri de receptori de dopamin\u0103 (D1, D2, D3, D4, D5). Dopamina se leag\u0103 de receptorii adrenergici alfa-1 \u0219i beta-1, av\u00e2nd formula molecular\u0103 C8H11NO2 Carbon 8 Hidrogen 11 Dioxid de Azot (NO2), Canonical SMILES, C1=CC(=C(C=C1CCN)O)O, \u0219i masa molecular\u0103 de 153.18 (cf. PubChem<\/em>).<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

\u00a0Figura 1. Structura chimic\u0103 2D a dopaminei (PubChem<\/em>)<\/strong><\/p>\n\n\n\n

Computed Properties (PubChem<\/em>)<\/strong><\/p>\n\n\n\n

Property Name<\/strong><\/td>Property Value<\/strong><\/td>Reference<\/strong><\/td><\/tr>
Molecular Weight<\/strong><\/td>153.18<\/strong><\/td>Computed by PubChem 2.1 (PubChem release 2021.05.07)<\/td><\/tr>
XLogP3<\/strong><\/td>-1<\/strong><\/td>Computed by XLogP3 3.0 (PubChem release 2021.05.07)<\/td><\/tr>
Hydrogen Bond Donor Count<\/td>3<\/td>Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)<\/td><\/tr>
Hydrogen Bond Acceptor Count<\/td>3<\/td>Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)<\/td><\/tr>
Rotatable Bond Count<\/strong><\/td>2<\/strong><\/td>Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)<\/td><\/tr>
Exact Mass<\/td>153.078978594<\/td>Computed by PubChem 2.1 (PubChem release 2021.05.07)<\/td><\/tr>
Monoisotopic Mass<\/td>153.078978594<\/td>Computed by PubChem 2.1 (PubChem release 2021.05.07)<\/td><\/tr>
Topological Polar Surface Area<\/strong><\/td>66.5 \u00c5\u00b2<\/strong><\/td>Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Ca substan\u021b\u0103 farmacologic\u0103, dopamina este indicat\u0103 \u00een afec\u021biuni cardiovasculare, stop cardiac (infarct miocardic) \u0219i interven\u021bii chirurgicale cardiace, cre\u0219terea tensiunii arteriale, tulbur\u0103ri de hipotensiune vascular\u0103, insuficien\u021b\u0103 renal\u0103, corectarea dezechilibrelor hemodinamice, traume, \u0219i chiar are efect antitumoral (Wick, 1982; PubChem<\/em>). Creierul con\u021bine sisteme neuronale separate care utilizeaz\u0103 3 catecolamine diferite – dopamin\u0103, norepinefrin\u0103 \u0219i epinefrin\u0103. Mai mult de jum\u0103tate din con\u021binutul catecolaminei din sistemul nervos central este dopamin\u0103, iar concentra\u021bia extrem de mare se g\u0103se\u0219te \u00een ganglionii bazali (\u00een special nucleul caudat), nucleul accumbens, tuberculul olfactiv, nucleul central al amigdalei, eminen\u021ba median\u0103 \u0219i c\u00e2mpurile restr\u00e2nse ale cortexului frontal (cf. Hardman, Limbird & Gilman, 2006, apud PubChem<\/em>). Dopamina este metabolizat\u0103 la nivelul ficatului \u0219i absorbit\u0103 \u00een intestinul sub\u021bire. Administrat\u0103 farmacologic, dopamina se elimin\u0103 \u00een mare parte, studiile ar\u0103t\u00e2nd c\u0103 aproximativ 80% din medicament este excretat prin urin\u0103 \u00een 24 de ore (DrugBank<\/em>).<\/p>\n\n\n\n

Conform studiilor din ultimii ani (Serafini, Pryce & Zachariou, 2020), circuitul dopaminergic mezolimbic are impact major \u00een diverse forme de durere acut\u0103 \u0219i cronic\u0103, prin c\u0103ile de semnalizare la nivelul sistemului de recompensare al creierului implicate \u00een manifest\u0103rile senzoriale \u0219i afective ale durerii. Dereglarea func\u021bion\u0103rii circuitului dopaminergic \u00een zonele active \u00een mecanismul recompensei (de la VTA, la Nucleu accumbens c\u0103tre PFC\/ cortexul prefrontal) poate promova totodat\u0103 tulbur\u0103rile afective comorbide \u0219i vulnerabilitatea la dependen\u021be. Aceste arii \u2013 zona tegmental\u0103 ventral\u0103 (VTA), nucleul accumbens (NAc), cortexul prefrontal (PFC), cortexul cingulat anterior (ACC) \u0219i amigdala \u2013 sunt implicate \u0219i \u00een gestionarea deciziilor executive, percep\u021bia emo\u021bional\u0103 \u0219i impulsul motiva\u021bional. Disfunc\u021biile din acest sistem pot contribui la boli neuropsihiatrice, inclusiv tulburare de depresie major\u0103 (MDD) \u0219i dependen\u021b\u0103 (Serafini et al.<\/em>, 2020).<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Figura 2.<\/strong> Date furnizate de studiile fMRI despre modific\u0103ri structurale \u0219i func\u021bionale din circuitele mezolimbice care stau la baza durerii cronice \u0219i a depresiei, \u00een mod independent \u0219i \u00een cadrul st\u0103rilor comorbide. Aceast\u0103 schem\u0103 eviden\u021biaz\u0103 schimb\u0103rile intra-regionale ale activit\u0103\u021bii colective de baz\u0103 \u0219i ale volumului materiei cenu\u0219ii \u00een cadrul popula\u021biilor de durere cronic\u0103, precum \u0219i modific\u0103ri ale conectivit\u0103\u021bii func\u021bionale \u00een cadrul popula\u021biilor de durere cronic\u0103, depresie \u0219i dependen\u021b\u0103. PFC=cortexul prefrontal; ACC=cortexul cingulat anterior; NAc=nucleus accumbens; VTA=aria tegmental\u0103 ventral\u0103; Am=amigdala (Serafini et al.<\/em>, 2020<\/a>).<\/p>\n\n\n\n

Cercet\u0103rile au ar\u0103tat c\u0103 etapele pre- \u0219i post-sinaptice ale neurotransmisiei dopaminergice sunt compromise \u00een timpul durerii cronice, precum \u0219i \u00een alte tulbur\u0103ri afective (vezi Figura 3). \u00cen conformitate cu activitatea VTA redus\u0103 la pacien\u021bii cu dureri cronice, un studiu pilot a constatat c\u0103 st\u0103rile de durere cronic\u0103 diminueaz\u0103 metabolismul presinaptic al dopaminei \u00een VTA, precum \u0219i \u00een girusul cingulat anterior \u0219i cortexul insular. Pe de alt\u0103 parte, pacien\u021bii cu dureri cronice de spate demonstreaz\u0103 o eliberare redus\u0103 de dopamin\u0103 ca r\u0103spuns la diverse traume sau provoc\u0103ri nocive. Muta\u021biile care reduc activitatea genelor de eliminare\/ echilibrare a dopaminei, cum ar fi COMT (catecol-O-metiltransferaza), par s\u0103 modifice sensibilitatea durerii prin modificarea r\u0103spunsurilor func\u021bionale ale receptorilor \u03bc-opioizi din NAc \u0219i alte circuite de procesare a durerii (Serafini et al., 2020).<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Figura 3.<\/strong> Muta\u021biile genetice care stau la baza modific\u0103rilor neurotransmisiei dopaminei mezolimbice codific\u0103 \u00een mod obi\u0219nuit proteinele implicate \u00een sinteza, clearance-ul \u0219i eliberarea dopaminei, precum \u0219i recaptarea pre-sinaptic\u0103 \u0219i legarea receptorilor post-sinaptici. Aceast\u0103 reprezentare prezint\u0103 exemple de muta\u021bii care modific\u0103 reglarea acestor gene, \u00eempreun\u0103 cu fenotipurile afective anormale respective. COMT=catecol-O-metiltransferaza; MAO-A=monoaminoxidaza A; DAT = transportor activ de dopamin\u0103; D1\/2\/3R=receptor de dopamin\u0103 D1\/2\/3; PT=toleranta la durere; NA=afect negativ; SA=risc de abuz de substan\u021be (Serafini et al.<\/em>, 2020).<\/p>\n\n\n\n

\u00cen contrast cu inhibi\u021bia mecanismelor postsinaptice inhibitoare \u00een popula\u021bia cu durere cronic\u0103, pacien\u021bii cu MDD (tulburare depresiv\u0103 major\u0103) pot prezenta o cre\u0219tere a disponibilit\u0103\u021bii D2\/D3R. Pacien\u021bii cu fibromialgie \u0219i depresie comorbid\u0103 au un poten\u021bial de legare D2\/D3R \u00een striatul ventral mai mare dec\u00e2t grupul de control (f\u0103r\u0103 depresie). Cannon \u015fi colab. (2009) a observat \u00een depresie o reducere a expresiei excitatorii D1R \u00een caudat, care inerveaz\u0103 puternic ACC, subliniind importan\u021ba activit\u0103\u021bii echilibrate a dopaminei \u00een reglarea proces\u0103rii afective. Similar cu observa\u021biile de la pacien\u021bii cu durere cronic\u0103, genele metabolismului dopaminei DAT-1 \u0219i COMT joac\u0103 un rol critic \u00een mediarea susceptibilit\u0103\u021bii la depresie. Un alt studiu a constatat c\u0103 polimorfismele care promoveaz\u0103 supraexprimarea, deci cre\u0219terea activit\u0103\u021bii acestor gene protejeaz\u0103 \u00eempotriva emo\u021bionalit\u0103\u021bii negative, sus\u021bin\u00e2nd \u0219i mai mult rolul dopaminei \u00een rezisten\u021ba la tulbur\u0103rile afective (Serafini et al.<\/em>, 2020).<\/p>\n\n\n\n

Similar cu durerea cronic\u0103 \u0219i depresia, func\u021bia D2\/D3R joac\u0103 un rol critic \u0219i \u00een vulnerabilitatea la dependen\u021be. S-a observat o sc\u0103dere a D2R la nivel striatal la indivizii dependen\u021bi de opiacee \u00een sevrajul precipitat de naloxon\u0103. Polimorfismul DRD2 rs1800497, care atenueaz\u0103 activitatea D2R, a fost, de asemenea, legat de vulnerabilitatea la dependen\u021ba de heroin\u0103 (Serafini et al.<\/em>, 2020).<\/p>\n\n\n\n

Concluzii<\/strong><\/p>\n\n\n\n

\u00cen concluzie, dovezile sugereaz\u0103 c\u0103 polimorfismele care conduc la o reducere a neurotransmisiei dopaminei promoveaz\u0103 at\u00e2t durerea cronic\u0103, c\u00e2t \u0219i depresia. \u00cen special, antidepresivele triciclice \u0219i SNRI (inhibitorii reabsorb\u021biei de serotonin\u0103-noradrenalin\u0103) promoveaz\u0103 activitatea dopaminei \u0219i amelioreaz\u0103 eficient simptomele senzoriale \u0219i afective ale durerii neuropatice.<\/p>\n\n\n\n

Av\u00e2nd \u00een vedere debutul lent \u0219i efectele secundare ale antidepresivelor, exist\u0103 o nevoie presant\u0103 de noi interven\u021bii terapeutice cu ac\u021biune rapid\u0103 care s\u0103 promoveze activitatea dopaminergic\u0103 pe calea de semnalizare a recompensei \u00een creier. Este deci necesar tratamentul psihoterapeutic de durat\u0103 care poate contribui la a reduce diferite tulbur\u0103ri cu substrat neuropsihologic \u0219i dependen\u021be, chiar la vindecarea multor tulbur\u0103ri afective.<\/p>\n\n\n\n

Referin\u021be bibliografice:<\/strong><\/p>\n\n\n\n

Berridge, K. C., & Kringelbach, M. L. (2015). Pleasure systems in the brain. Neuron<\/em>, 86<\/em>(3), 646\u2013664. https:\/\/doi.org\/10.1016\/j.neuron.2015.02.018.<\/p>\n\n\n\n

Fordahl, S. C., Locke, J. L., & Jones, S. R. (2016). High fat diet augments amphetamine sensitization in mice: Role of feeding pattern, obesity, and dopamine terminal changes. Neuropharmacology<\/em>, 109<\/em>, 170\u2013182. https:\/\/doi.org\/10.1016\/j.neuropharm.2016.06.006.        <\/p>\n\n\n\n

Han, W., Tellez, L. A., Perkins, M. H., Perez, I. O., Qu, T., Ferreira, J., Ferreira, T. L., Quinn, D., Liu, Z. W., Gao, X. B., Kaelberer, M. M., Boh\u00f3rquez, D. V., Shammah-Lagnado, S. J., de Lartigue, G., & de Araujo, I. E. (2018). A Neural Circuit for Gut-Induced Reward. Cell<\/em>, 175<\/em>(3), 665\u2013678.e23. https:\/\/doi.org\/10.1016\/j.cell.2018.08.049.<\/p>\n\n\n\n

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman.(2006). Goodman and Gilman\u2019s The Pharmacological Basis of Therapeutics<\/em>. 11th ed. New York, NY: McGraw-Hill.<\/p>\n\n\n\n

Kessler, Robert M.; Peter H. Hutson, Barry K. Herman, Marc N. Potenza. (2016). The neurobiological basis of binge-eating disorder. Neuroscience & Biobehavioral Reviews<\/em>, Vol. 63: 223-238, https:\/\/doi.org\/10.1016\/j.neubiorev.2016.01.013.<\/p>\n\n\n\n

Nathan, P. J., O’Neill, B. V., Napolitano, A., & Bullmore, E. T. (2011). Neuropsychiatric adverse effects of centrally acting antiobesity drugs. CNS neuroscience & therapeutics<\/em>, 17<\/em>(5), 490\u2013505. https:\/\/doi.org\/10.1111\/j.1755-5949.2010.00172.x.<\/p>\n\n\n\n

National Center for Biotechnology Information (2022). PubChem<\/em> Compound Summary for CID 681, Dopamine. Retrieved January 2, 2022 from https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Dopamine.<\/p>\n\n\n\n

Pitts, E. G., Stowe, T. A., Christensen, B. A., & Ferris, M. J. (2020). Comparing dopamine release, uptake, and D2 autoreceptor function across the ventromedial to dorsolateral striatum in adolescent and adult male and female rats. Neuropharmacology<\/em>, 175<\/em>, 108163. https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108163.<\/p>\n\n\n\n

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Serafini, R. A., Pryce, K. D., & Zachariou, V. (2020). The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities. Biological Psychiatry<\/em>, 87<\/em>(1), 64\u201373. https:\/\/doi.org\/10.1016\/j.biopsych.2019.10.018.<\/p>\n\n\n\n

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\"\"<\/figure>","protected":false},"excerpt":{"rendered":"

Citation: Ceciu, Ramona L. 2022. Rolul Dopaminei \u00een Creier \u0219i S\u0103n\u0103tate. Life and Mind Art Research journal, no. 2, August. Paper initially presented at the University of Bucharest on 8 Jan. 2022. (Please include the link when you cite this article and add the access date). Introducere Dopamina este unul dintre cei mai cunoscu\u021bi neurotransmi\u021b\u0103tori, […]<\/p>\n","protected":false},"author":1,"featured_media":151,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6],"tags":[],"class_list":["post-1","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-scholarly-presentations-publications"],"_links":{"self":[{"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/posts\/1","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/comments?post=1"}],"version-history":[{"count":1,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/posts\/1\/revisions"}],"predecessor-version":[{"id":152,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/posts\/1\/revisions\/152"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/media\/151"}],"wp:attachment":[{"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/media?parent=1"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/categories?post=1"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeandmindart.com\/en\/wp-json\/wp\/v2\/tags?post=1"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}