Pathophysiology of Addiction

Öz

The use of alcohol, tobacco and illegal drugs, apart from causing health problems, also  increases the loss of labor and  tendency to crime. Addiction not only occurs against substances, but also varies as gambling, internet, eating, work, exercise and shopping addiction. Although it can be treated, it is characterized by the high frequency of recurrences. Brain parts, environmental and individual factors, genetic characteristics play a major role in the development of addiction. While the substance use causes addiction, they lead to changes in the reward system, decision-making and memory related brain parts. The mesocorticolimbic system is an important part of the reward system. Dopamine is the main neurotransmitter in this system. Behaviors such as gambling, internet use, eating and shopping also increase the release of dopamine by activating the reward pathway, such as substances that cause addiction. Disorders in the mesocorticolimbic pathway and associated brain parts play a role in the formation of addiction. Apart from the dopaminergic mesocorticolimbic system, other systems and neurotansmitters are thought to be effective in the development of addiction.

Anahtar Kelimeler

• Alcohol,Drug Addiction,Mesocorticolimbic System,Nicotine

Bağımlılığın Patofizyolojisi

Öz

Alkol, sigara ve yasaklı maddelerin kullanımı, yol açtığı sağlık problemlerinin yanında, iş gücünde kayba ve suça eğilimde artmaya sebep olmasıyla, ortaya çıkan maddi ve manevi hasarı daha da arttırmaktadır. Bağımlılık sadece maddelere karşı oluşmamakta, kumar, internet, yeme, iş, egzersiz, alışveriş bağımlılığı gibi türlerle de günümüzde giderek çeşitliliği artmaktadır. Tedavi edilebilmesine rağmen, nükslerin sıklığı ile karakterizedir. Beyin yapıları, çevresel ve kişiye bağlı etkenler, genetik özellikler bağımlılık gelişiminde rol oynamaktadır. Kullanılan maddeler bağımlılık oluşumuna sebep olurken, ödül sistemi, karar verme, hafıza ile ilgili beyin yapılarında değişikliklere yol açmaktadır. Mezokortikolimbik sistem, ödül sisteminin önemli bir parçasını oluşturmaktadır. Dopamin bu sistemdeki ana nörotransmiterdir. Kumar, internet kullanımı, yeme, alışveriş gibi davranışlar da, bağımlılığa yol açan maddeler gibi ödül yolağını aktive ederek, DA salımını arttırmaktadır. Mezokortikolimbik yolak ve bağlantılı beyin yapılarındaki bozukluklar bağımlılık oluşumunda rol oynamaktadır. Dopaminerjik mezokortikolimbik sistem dışında, başka sistem ve nörotansmiterlerin de bağımlılık gelişiminde etkili olduğu düşünülmektedir

Anahtar Kelimeler

• Alkol,Madde Bağımlılığı,Mezokortikolimbik Sistem,Nikotin

Kaynakça

1. 1. American Psychiatric Association and American Psychiatric Association DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5 Washington, DC American Psychiatric Association, 2013.
2. 2. Harricharan R, Abboussi O, Daniels WMU. Addiction: A dysregulation of satiety and inflammatory processes. Prog Brain Res. 2017;235:65-91.
3. 3. Koob GF. Neurobiological substrates for the dark side of compulsivity in addiction. Neuropharmacology. 2009;56 Suppl 1:18-31.
4. 4. Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. The Lancet Psychiatry. Lancet Psychiatry. 2016;3(8):760-73.
5. 5. Volkow ND, Morales M. The Brain on Drugs: From Reward to Addiction. Cell. 2015;162(4):712-25.
6. 6. UNODC. World Drug Report 2017. United Nations Office on Drugs and Crime. 2017.
7. 7. van den Heuvel LL. Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications 4th eds. J Child Adolesc Ment Heal. 2014.
8. 8. Pariyadath V, Gowin JL, Stein EA. Resting state functional connectivity analysis for addiction medicine: From individual loci to complex networks Prog Brain Res. 2016;224:155-73.

9. 9. Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci. 1992;13(5):177-84.
10. 10. Margolis EB, Toy B, Himmels P, Morales M, Fields HL. Identification of rat ventral tegmental area GABAergic neurons. PLoS One. 2012;7(7): e42365.
11. 11. Pistillo F, Clementi F, Zoli M, Gotti C. Nicotinic, glutamatergic and dopaminergic synaptic transmission and plasticity in the mesocorticolimbic system: Focus on nicotine effects. Prog Neurobiol. 2015;124:1-27.
12. 12. Tritsch NX, Ding JB, Sabatini BL. Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature. 2012;11;490(7419):262-6.
13. 13. Jaworski JN, Kozel MA, Philpot KB, Kuhar MJ. Intra-accumbal injection of CART (cocaine-amphetamine regulated transcript) peptide reduces cocaine-induced locomotor activity. J Pharmacol Exp Ther. 2003;307(3):1038-44.
14. 14. Hubert GW, Jones DC, Moffett MC, Rogge G, Kuhar MJ. CART peptides as modulators of dopamine and psychostimulants and interactions with the mesolimbic dopaminergic system. Biochem Pharmacol. 2008;75(1):57–62.
15. 15. Yager LM, Garcia AF, Wunsch AM, Ferguson SM. The ins and outs of the striatum: role in drug addiction. Neuroscience. 2015;20;301:529-41.
16. 16. Howard CD, Li H, Geddes CE, Jin X. Dynamic Nigrostriatal Dopamine Biases Action Selection. Neuron. 2017;22:93(6):1436-50.
17. 17. Koob GF, Everitt BJ, Robbins TW. Reward, Motivation, and Addiction. In: Fundamental Neuroscience: 4th eds. 2013.
18. 18. Turton S, Lingford-Hughes A. Neurobiology and principles of addiction and tolerance. Medicine (United Kingdom). 2016;44(12):693–6.
19. 19. Nestler EJ. Is there a common molecular pathway for addiction? Nat Neurosci. 2005;8(11):1445-9.
20. 20. Koylu EO, Balkan B, Kuhar MJ, Pogun S. Cocaine and amphetamine regulated transcript (CART) and the stress response. Peptides. 2006;27(8):1956–69.
21. 21. Balkan B, Keser A, Gozen O, et al. Forced swim stress elicits region-specific changes in CART expression in the stress axis and stress regulatory brain areas. Brain Res. 2012;1432:56–65.
22. 22. Sinha R. How does stress increase risk of drug abuse and relapse? Psychopharmacology 2001;158(4):343-59.
23. 23. Merikangas KR, Mehta RL, Molnar BE et al. Comorbidity of substance use disorders with mood and anxiety disorders: Results of the international Consortium in Psychiatric Epidemiology. Addict Behav. 1998;23(6):893-907.
24. 24. Department of Health. The Public Health Outcomes Framework for England, 2013-2016. Dep Heal. 2012;1–3.
25. 25. Klink R, de Kerchove d’Exaerde a, Zoli M, Changeux JP. Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci. 2001;21(5):1452–63.
26. 26. Champtiaux N, Gotti C, Cordero-Erausquin M et al. Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J Neurosci. 2003;23(21):7820–9.
27. 27. Picciotto MR, Corrigall WA. Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics. J Neurosci. 2002;22(9):3338–41.
28. 28. Wonnacott S, Kaiser S, Mogg A, Soliakov L, Jones IW. Presynaptic nicotinic receptors modulating dopamine release in the rat striatum. Eur J Pharmacol. 2000;393(1–3):51–8.
29. 29. Koob GF. A role for brain stress systems in addiction. Neuron. 2008;59(1):11–34.
30. 30. Greenbaum L, Lerer B. Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions. Mol Psychiatry. 2009;14(10):912-45.
31. 31. Suarez S V, Amadon A, Giacomini E, et al. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: A BOLD fMRI study. Psychopharmacology. 2009;202(4):599–610.
32. 32. Benwell MEM, Balfour DJK, Birrell CE. Desensitization of the nicotine‐induced mesolimbic dopamine responses during constant infusion with nicotine. Br J Pharmacol. 1995;114(2):454–60.
33. 33. Kenny PJ, Markou A. Nicotine Self-Administration Acutely Activates Brain Reward Systems and Induces a Long-Lasting Increase in Reward Sensitivity. Neuropsychopharmacology. 2005;31(6):1203–11.
34. 34. Caille S, Guillem K, Cador M, Manzoni O, Georges F. Voluntary nicotine consumption triggers in vivo potentiation of cortical excitatory drives to midbrain dopaminergic neurons. J Neurosci. 2009;29(33):10410–5.
35. 35. Cadoni C, Di Chiara G. Differential changes in accumbens shell and core dopamine in behavioral sensitization to nicotine. Eur J Pharmacol. 2000;17:387(3):R23-5.
36. 36. Nisell M, Nomikos GG, Hertel P, Panagis G, Svensson TH. Condition-independent sensitization of locomotor stimulation and mesocortical dopamine release following chronic nicotine treatment in the rat. Synapse. 1996;22(4):369–81.
37. 37. Balfour DJK. The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res. 2004;6(6):899–912.
38. 38. Squeglia LM, Jacobus J, Tapert SF. The effect of alcohol use on human adolescent brain structures and systems. Handb Clin Neurol. 2014;125:501-10.
39. 39. Koob GF, Colrain IM. Alcohol use disorder and sleep disturbances: a feed-forward allostatic framework. Neuropsychopharmacology. 2020;45(1):141-65.
40. 40. Uhl GR, Koob GF, Cable J. The neurobiology of addiction. Ann N Y Acad Sci. 2019;1451(1):5-28.
41. 41. Björklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci. 2007;30(5):194-202.
42. 42. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology.2010;35(1):217–38.