^Nestler, Eric J.; Malenka, Robert C. Chapter 15: Reinforcement and Addictive Disorders. Molecular neuropharmacology : a foundation for clinical neuroscience 2nd ed. New York: McGraw-Hill Medical. 2009: 364–375. ISBN 978-0-07-164119-7. OCLC 273018757. 引文格式1维护：冗余文本 (link)
^ 2.02.12.22.32.42.52.6Nestler, Eric J. Cellular basis of memory for addiction. Dialogues in Clinical Neuroscience. 2013-12, 15 (4): 431–443. ISSN 1294-8322. PMC 3898681. PMID 24459410. doi:10.31887/DCNS.2013.15.4/enestler.
^ 3.03.1Glossary. Icahn School of Medicine. [2021-04-29].
^Volkow, Nora D.; Koob, George F.; McLellan, A. Thomas. Longo, Dan L. , 编. Neurobiologic Advances from the Brain Disease Model of Addiction. New England Journal of Medicine. 2016-01-28, 374 (4): 363–371. ISSN 0028-4793. PMC 6135257. PMID 26816013. doi:10.1056/NEJMra1511480（英语）. 引文格式1维护：PMC格式 (link)
^Angres DH, Bettinardi-Angres K. The disease of addiction: origins, treatment, and recovery. Dis Mon. October 2008, 54 (10): 696–721. PMID 18790142. doi:10.1016/j.disamonth.2008.07.002.
^American Society for Addiction Medicine. Definition of Addiction. 2012 [2013-06-25]. （原始内容于2018-06-14）.
^Clinical and Research Implications of Gambling Disorder in DSM-5. [2017-05-04]. （原始内容于2021-08-09）.
^American Psychiatric Association. Substance-Related and Addictive Disorders (PDF). American Psychiatric Publishing: 1–2. 2013 [10 July 2015]. （原始内容 (PDF)于2015-08-15）. Additionally, the diagnosis of dependence caused much confusion. Most people link dependence with "addiction" when in fact dependence can be a normal body response to a substance.
^Malenka RC, Nestler EJ, Hyman SE. Chapter 1: Basic Principles of Neuropharmacology. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 4. ISBN 9780071481274. Drug abuse and addiction exact an astoundingly high financial and human toll on society through direct adverse effects, such as lung cancer and hepatic cirrhosis, and indirect adverse effects—for example, accidents and AIDS—on health and productivity.
^ 10.010.1KR Merikangas KR, McClair VL. Epidemiology of Substance Use Disorders. Hum. Genet. June 2012, 131 (6): 779–789. PMC 4408274. PMID 22543841. doi:10.1007/s00439-012-1168-0.
^AMERICAN BOARD OF MEDICAL SPECIALTIES RECOGNIZES THE NEW SUBSPECIALTY OF ADDICTION MEDICINE (PDF). American Board of Addiction Medicine. 14 March 2016 [3 April 2016]. （原始内容 (PDF)于2021-03-21）.
^Morse RM, Flavin DK. The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism. JAMA. August 1992, 268 (8): 1012–4. PMID 1501306. doi:10.1001/jama.1992.03490080086030.
^Marlatt GA, Baer JS, Donovan DM, Kivlahan DR. Addictive behaviors: etiology and treatment. Annu Rev Psychol. 1988, 39: 223–52. PMID 3278676. doi:10.1146/annurev.ps.39.020188.001255.
^ 14.014.114.214.314.4Ruffle JK. Molecular neurobiology of addiction: what's all the (Δ)FosB about?. Am. J. Drug Alcohol Abuse. November 2014, 40 (6): 428–437. PMID 25083822. doi:10.3109/00952990.2014.933840. The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. ... Conclusions ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a ‘‘molecular switch’’ (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
^ 15.015.115.2Olsen CM. Natural rewards, neuroplasticity, and non-drug addictions. Neuropharmacology. December 2011, 61 (7): 1109–1122. PMC 3139704. PMID 21459101. doi:10.1016/j.neuropharm.2011.03.010. Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)." Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers （页面存档备份，存于互联网档案馆）"
^American Society for Addiction Medicine. Definition of Addiction. 2012 [2013-06-25]. （原始内容于2018-06-14）.
^Taylor SB, Lewis CR, Olive MF. The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans. Subst. Abuse Rehabil. February 2013, 4: 29–43. PMC 3931688. PMID 24648786. doi:10.2147/SAR.S39684. Initial drug use can be attributed to the ability of the drug to act as a reward (ie, a pleasurable emotional state or positive reinforcer), which can lead to repeated drug use and dependence.8,9 A great deal of research has focused on the molecular and neuroanatomical mechanisms of the initial rewarding or reinforcing effect of drugs of abuse. ... At present, no pharmacological therapy has been approved by the FDA to treat psychostimulant addiction. Many drugs have been tested, but none have shown conclusive efficacy with tolerable side effects in humans.172 ...A new emphasis on larger-scale biomarker, genetic, and epigenetic research focused on the molecular targets of mental disorders has been recently advocated.212 In addition, the integration of cognitive and behavioral modification of circuit-wide neuroplasticity (ie, computer-based training to enhance executive function) may prove to be an effective adjunct-treatment approach for addiction, particularly when combined with cognitive enhancers.198,213–216 Furthermore, in order to be effective, all pharmacological or biologically based treatments for addiction need to be integrated into other established forms of addiction rehabilitation, such as cognitive behavioral therapy, individual and group psychotherapy, behavior-modification strategies, twelve-step programs, and residential treatment facilities.
^ 18.018.118.2Biliński P, Wojtyła A, Kapka-Skrzypczak L, Chwedorowicz R, Cyranka M, Studziński T. Epigenetic regulation in drug addiction. Ann. Agric. Environ. Med. 2012, 19 (3): 491–496. PMID 23020045. For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription
^Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat. Rev. Neurosci. November 2011, 12 (11): 623–637. PMC 3272277. PMID 21989194. doi:10.1038/nrn3111. ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.
^Vassoler FM, Sadri-Vakili G. Mechanisms of transgenerational inheritance of addictive-like behaviors. Neuroscience. 2014, 264: 198–206. PMC 3872494. PMID 23920159. doi:10.1016/j.neuroscience.2013.07.064. The environment also plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time (UNODC, 2012). Therefore, both genetics and the environment contribute to an individual's vulnerability to become addicted following an initial exposure to drugs of abuse.
^Slade, T.; Johnston, A.; Teesson, M.; Whiteford, H.; Burgess, P.; Pirkis, J.; Saw, S. The Mental Health of Australians 2: Substance Use Disorders in Australia (PDF). Department of Health and Ageing, Canberra. May 2009 [2017-05-02]. （原始内容 (PDF)于2020-08-18）.
成瘾, 上瘾, 重定向至此, 关于2016年中国大陆同志题材网络剧集, 请见, 上癮, 網路劇, 维基百科中的醫學内容仅供参考, 並不能視作專業意見, 如需獲取醫療幫助或意見, 请咨询专业人士, 詳見醫學聲明, 此條目需要精通或熟悉醫學的编者参与及协助编辑, 請邀請適合的人士改善本条目, 更多的細節與詳情請參见討論頁, addictionbrain, positron, emission, tomography, images, that, compare, brain, metabolism, healthy, . 上瘾 重定向至此 关于2016年中国大陆同志题材网络剧集 请见 上癮 網路劇 维基百科中的醫學内容仅供参考 並不能視作專業意見 如需獲取醫療幫助或意見 请咨询专业人士 詳見醫學聲明 此條目需要精通或熟悉醫學的编者参与及协助编辑 請邀請適合的人士改善本条目 更多的細節與詳情請參见討論頁 成瘾AddictionBrain positron emission tomography images that compare brain metabolism in a healthy individual and a cocaine addict类型行為 健康問題 习惯分类和外部资源醫學專科成癮精神病學 英语 Addiction psychiatry 成癮醫學 英语 Addiction medicine 编辑此条目的维基数据 成癮及生理 心理依賴 的相關術語詞彙表 1 2 3 4 成瘾 腦部失調的情形 特徵是會強迫性的接觸犒赏刺激 不去考慮其帶來的負面結果 成瘾行为 具有犒赏性及正向增強效應的行為 成瘾药物 具有犒赏性及正向增強效應的藥物 依赖性 之前曾頻繁接觸刺激源 例如藥物攝取 中斷接觸後出現戒斷症狀的情形 药物敏化或逆耐药性 在固定藥物劑量的情形下重複給藥 而相同劑量的藥物效果增強的情形 藥物戒斷 在重複藥物使用後停藥 出現的症狀 生理依赖 出現持續生理戒斷症狀 例如疲勞及震顫性譫妄 的依赖性 心理依赖 出現情緒或是精神戒斷症狀 例如煩躁及失乐 的依赖性 增强刺激 特定類型的刺激 接觸後會增加再接觸此刺激的可能性 犒赏刺激 特定類型的刺激 大腦會認為此刺激是正向的 會想再進行的 敏化作用 重複接受某一刺激後產生的刺激增強性反應 物質使用疾患 使用特定物質 而且造成臨床上或是功能上的損傷或是困境的情形 藥物耐受性 重複接受某一藥物後產生的藥物降低性反應查论编成瘾 英語 addiction 是指一種重複性的強迫行為 即使這些行為已知可能造成不良後果的情形下 仍然被持續重複 5 這種行為可能因中樞神經系統功能失調造成 重複這些行為也可以反過來造成神經功能受損 6 瘾可用于描述生理依賴或者过度的心理依赖 例如物質依賴 药物滥用 即俗称的滥药 毒瘾 酒瘾 烟瘾 性癮 或是持續出現特定行為 赌 暴食 网瘾 赌瘾 官瘾 财迷 工作狂 暴食症 跟蹤狂 偷窃狂 整形迷恋 购物狂 發表廢文甚至恋物癖等 是生理或者心理上 甚至是同時具备的一种依赖症 瘾有分為物質成癮及行為成癮 英语 Behavioral addiction 行為成癮是和物质无关的强迫症 如赌瘾和网瘾 在这几种通常的用法中 瘾是描述一种某人高频率反复从事可能对其身心健康和社交生活有害的活动的一种强迫行为 而精神疾病診斷與統計手冊的第五版DSM 5中有將赌瘾 gambling disorder 列入 7 有時成瘾 addiction 會和物質依賴 substance dependence 混淆 8 兩者主要的不同是 物質依賴者在中斷物質使用後 會出現戒斷症狀 甚至造成更多的使用該物質 而成瘾是強制性的攝取某種物質或從事特定行為 不一定有戒斷症狀 物質成瘾會對個人和社會帶來顯著的影響 包括成癮物質帶來的直接影響 伴隨的醫療費用 長期的併發症 例如吸煙可能造成的肺癌 酒癮可能會有的肝硬化 靜脈注射甲基苯丙胺會出現的冰毒嘴 英语 meth mouth 症狀 神经可塑性 因為經驗原因引起大腦結構的改變 帶來的影響 以及後續生產力的下降 9 10 11 成瘾的典型現象包括對於物質或是行為的無法控制及過度關注 雖然有不良結果 卻仍然繼續攝取成瘾物質或從事特定行為的情形 12 伴隨著成癮的習慣或是行為模式通常是立即性的滿足 短期回報 及延遲出現的不良影響 長期不良結果 13 有时在口语上 瘾也用于指某些人的一些癖好 例如读书 收集 集邮 看电视 玩游戏 购物 工作 上网 运动及进食等 不過在本条目中 瘾主要是被用于滥用药物和物质滥用问题 也就是有生理依賴或者过度心理依赖的行為 目录 1 醫學觀點 2 藥物成癮 3 流行病學 4 参见 5 腳註 6 參考資料 7 外部連結醫學觀點 编辑医学上 成癮是腦中犒賞系統在基因转录及表觀遺傳機制上出現的失調 成癮有許多心理上的原因 但依生理來說 是在長期暴露在高度的成癮刺激原 addictive stimulus 例如嗎啡 可卡因 性交 賭博等 後出現的情形 2 14 15 重複暴露在成癮刺激原是主要導致成癮以及維持成癮現象的主要病理因素 2 16 成癮刺激原有二個特性 一個是其正向增強 接觸後會增加再去進行類似行為的可能性 另一個是內在犒賞 認為此物質或是行為有趣 會想要再去進行 2 3 17 转录因子DFosB是各種成癮 行為成癮或物質成癮 發展中的關鍵成份及共同因素 14 15 18 19 二十多年針對DFosB在成瘾當中的研究 結果指出成瘾的出現以及伴隨的强迫行为加剧或减弱 都和伏隔核中D1型中度多刺神經元中DFosB的基因過度表現 genetic overexpression 有關 2 14 15 18 因為DFosB基因表現與成瘾之間有因果關係 DFosB在臨床前研究 英语 preclinical research 中常作為成瘾的生物標記 2 14 18 DFosB在這些神經元的表現一方面會直接調高藥物Self administration 英语 Self administration 及犒賞敏感度 也會透過正增強達到這些效果 另一方面也會降低對厭惡 aversion 的敏感度 note 1 2 14 腹側被蓋區被認為與神經生物學理論中的成癮現象有關 20 21 藥物成癮 编辑主条目 物質依賴 診斷藥物成癮可診斷為生理成癮 成癮有增加或減退跡象 和沒有成癮 DSM IV中介紹的包括 303 90 酒精依賴 304 00 鴉片依賴 304 10 鎮靜劑依賴 催眠藥依賴 或抗焦慮藥依賴 包括苯二氮平類藥物成瘾和巴比妥依賴 304 20 可卡因依賴 304 30 大麻依賴 304 40 安非他命依賴 或似安非他命類 304 50 致幻剂依賴 304 60 鼻吸劑 英语 Inhalant 依賴 304 80 多種物質依賴 304 90 苯環利定 英语 Phencyclidine 或似苯環利定類 依賴 304 90 其他 或未知 物質依賴 305 10 尼古丁依賴流行病學 编辑因為文化的不同 特定時間內出現藥物成癮或是行為成癮的比例 即患病率 會隨時代及國家而不同 也會因為年齡層 社會經濟地位等人口学資料而不同 22 澳洲2009年的藥物濫用患病率為5 1 23 依照美國2011年在青少年中抽樣的結果來看 其酒癮及非法藥物濫用的lifetime prevalence 個體從出生後 一直到接受抽樣之前 曾出現過的比例 分別是8 及2 3 10 参见 编辑毒品 吸烟 酗酒 檳榔 赌博 性成癮 网络成瘾症 精神鸦片 匿名戒酒會 理性成癮 固著腳註 编辑 降低對厭惡的敏感度 簡單來說 就是讓個人的行為比較不會被其不想要的負面結果而影 比較不因為有可能負面結果而不去做該行為參考資料 编辑 Nestler Eric J Malenka Robert C Chapter 15 Reinforcement and Addictive Disorders Molecular neuropharmacology a foundation for clinical neuroscience 2nd ed New York McGraw Hill Medical 2009 364 375 ISBN 978 0 07 164119 7 OCLC 273018757 引文格式1维护 冗余文本 link 2 0 2 1 2 2 2 3 2 4 2 5 2 6 Nestler Eric J Cellular basis of memory for addiction Dialogues in Clinical Neuroscience 2013 12 15 4 431 443 ISSN 1294 8322 PMC 3898681 PMID 24459410 doi 10 31887 DCNS 2013 15 4 enestler 3 0 3 1 Glossary Icahn School of Medicine 2021 04 29 Volkow Nora D Koob George F McLellan A Thomas Longo Dan L 编 Neurobiologic Advances from the Brain Disease Model of Addiction New England Journal of Medicine 2016 01 28 374 4 363 371 ISSN 0028 4793 PMC 6135257 PMID 26816013 doi 10 1056 NEJMra1511480 英语 引文格式1维护 PMC格式 link Angres DH Bettinardi Angres K The disease of addiction origins treatment and recovery Dis Mon October 2008 54 10 696 721 PMID 18790142 doi 10 1016 j disamonth 2008 07 002 American Society for Addiction Medicine Definition of Addiction 2012 2013 06 25 原始内容存档于2018 06 14 Clinical and Research Implications of Gambling Disorder in DSM 5 2017 05 04 原始内容存档于2021 08 09 American Psychiatric Association Substance Related and Addictive Disorders PDF American Psychiatric Publishing 1 2 2013 10 July 2015 原始内容存档 PDF 于2015 08 15 Additionally the diagnosis of dependence caused much confusion Most people link dependence with addiction when in fact dependence can be a normal body response to a substance Malenka RC Nestler EJ Hyman SE Chapter 1 Basic Principles of Neuropharmacology Sydor A Brown RY 编 Molecular Neuropharmacology A Foundation for Clinical Neuroscience 2nd New York McGraw Hill Medical 2009 4 ISBN 9780071481274 Drug abuse and addiction exact an astoundingly high financial and human toll on society through direct adverse effects such as lung cancer and hepatic cirrhosis and indirect adverse effects for example accidents and AIDS on health and productivity 10 0 10 1 KR Merikangas KR McClair VL Epidemiology of Substance Use Disorders Hum Genet June 2012 131 6 779 789 PMC 4408274 PMID 22543841 doi 10 1007 s00439 012 1168 0 AMERICAN BOARD OF MEDICAL SPECIALTIES RECOGNIZES THE NEW SUBSPECIALTY OF ADDICTION MEDICINE PDF American Board of Addiction Medicine 14 March 2016 3 April 2016 原始内容存档 PDF 于2021 03 21 Morse RM Flavin DK The definition of alcoholism The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism JAMA August 1992 268 8 1012 4 PMID 1501306 doi 10 1001 jama 1992 03490080086030 Marlatt GA Baer JS Donovan DM Kivlahan DR Addictive behaviors etiology and treatment Annu Rev Psychol 1988 39 223 52 PMID 3278676 doi 10 1146 annurev ps 39 020188 001255 14 0 14 1 14 2 14 3 14 4 Ruffle JK Molecular neurobiology of addiction what s all the D FosB about Am J Drug Alcohol Abuse November 2014 40 6 428 437 PMID 25083822 doi 10 3109 00952990 2014 933840 The strong correlation between chronic drug exposure and DFosB provides novel opportunities for targeted therapies in addiction 118 and suggests methods to analyze their efficacy 119 Over the past two decades research has progressed from identifying DFosB induction to investigating its subsequent action 38 It is likely that DFosB research will now progress into a new era the use of DFosB as a biomarker ConclusionsDFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure The formation of DFosB in multiple brain regions and the molecular pathway leading to the formation of AP 1 complexes is well understood The establishment of a functional purpose for DFosB has allowed further determination as to some of the key aspects of its molecular cascades involving effectors such as GluR2 87 88 Cdk5 93 and NFkB 100 Moreover many of these molecular changes identified are now directly linked to the structural physiological and behavioral changes observed following chronic drug exposure 60 95 97 102 New frontiers of research investigating the molecular roles of DFosB have been opened by epigenetic studies and recent advances have illustrated the role of DFosB acting on DNA and histones truly as a molecular switch 34 As a consequence of our improved understanding of DFosB in addiction it is possible to evaluate the addictive potential of current medications 119 as well as use it as a biomarker for assessing the efficacy of therapeutic interventions 121 122 124 Some of these proposed interventions have limitations 125 or are in their infancy 75 However it is hoped that some of these preliminary findings may lead to innovative treatments which are much needed in addiction 15 0 15 1 15 2 Olsen CM Natural rewards neuroplasticity and non drug addictions Neuropharmacology December 2011 61 7 1109 1122 PMC 3139704 PMID 21459101 doi 10 1016 j neuropharm 2011 03 010 Functional neuroimaging studies in humans have shown that gambling Breiter et al 2001 shopping Knutson et al 2007 orgasm Komisaruk et al 2004 playing video games Koepp et al 1998 Hoeft et al 2008 and the sight of appetizing food Wang et al 2004a activate many of the same brain regions i e the mesocorticolimbic system and extended amygdala as drugs of abuse Volkow et al 2004 Cross sensitization is also bidirectional as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA As described for food reward sexual experience can also lead to activation of plasticity related signaling cascades The transcription factor delta FosB is increased in the NAc PFC dorsal striatum and VTA following repeated sexual behavior Wallace et al 2008 Pitchers et al 2010b This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance and NAc blockade of delta FosB attenuates this behavior Hedges et al 2009 Pitchers et al 2010b Further viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience Hedges et al 2009 In some people there is a transition from normal to compulsive engagement in natural rewards such as food or sex a condition that some have termed behavioral or non drug addictions Holden 2001 Grant et al 2006a In humans the role of dopamine signaling in incentive sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs This syndrome is characterized by a medication induced increase in or compulsive engagement in non drug rewards such as gambling shopping or sex Evans et al 2006 Aiken 2007 Lader 2008 Table 1 Summary of plasticity observed following exposure to drug or natural reinforcers 页面存档备份 存于互联网档案馆 American Society for Addiction Medicine Definition of Addiction 2012 2013 06 25 原始内容存档于2018 06 14 Taylor SB Lewis CR Olive MF The neurocircuitry of illicit psychostimulant addiction acute and chronic effects in humans Subst Abuse Rehabil February 2013 4 29 43 PMC 3931688 PMID 24648786 doi 10 2147 SAR S39684 Initial drug use can be attributed to the ability of the drug to act as a reward ie a pleasurable emotional state or positive reinforcer which can lead to repeated drug use and dependence 8 9 A great deal of research has focused on the molecular and neuroanatomical mechanisms of the initial rewarding or reinforcing effect of drugs of abuse At present no pharmacological therapy has been approved by the FDA to treat psychostimulant addiction Many drugs have been tested but none have shown conclusive efficacy with tolerable side effects in humans 172 A new emphasis on larger scale biomarker genetic and epigenetic research focused on the molecular targets of mental disorders has been recently advocated 212 In addition the integration of cognitive and behavioral modification of circuit wide neuroplasticity ie computer based training to enhance executive function may prove to be an effective adjunct treatment approach for addiction particularly when combined with cognitive enhancers 198 213 216 Furthermore in order to be effective all pharmacological or biologically based treatments for addiction need to be integrated into other established forms of addiction rehabilitation such as cognitive behavioral therapy individual and group psychotherapy behavior modification strategies twelve step programs and residential treatment facilities 18 0 18 1 18 2 Bilinski P Wojtyla A Kapka Skrzypczak L Chwedorowicz R Cyranka M Studzinski T Epigenetic regulation in drug addiction Ann Agric Environ Med 2012 19 3 491 496 PMID 23020045 For these reasons DFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre prefrontal cortex and other regions of the limbic system This is reflected in the increased stable and long lasting level of sensitivity to cocaine and other drugs and tendency to relapse even after long periods of abstinence These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken In this way the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3 A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine This depends on DFosB inhibiting G9a gene expression i e H3K9me2 synthesis which in turn inhibits transcription factors for DFosB For this reason the observed hyper expression of G9a which ensures high levels of the dimethylated form of histone H3 eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks DFosB transcription Robison AJ Nestler EJ Transcriptional and epigenetic mechanisms of addiction Nat Rev Neurosci November 2011 12 11 623 637 PMC 3272277 PMID 21989194 doi 10 1038 nrn3111 DFosB has been linked directly to several addiction related behaviors Importantly genetic or viral overexpression of DJunD a dominant negative mutant of JunD which antagonizes DFosB and other AP 1 mediated transcriptional activity in the NAc or OFC blocks these key effects of drug exposure14 22 24 This indicates that DFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure DFosB is also induced in D1 type NAc MSNs by chronic consumption of several natural rewards including sucrose high fat food sex wheel running where it promotes that consumption14 26 30 This implicates DFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive like states 2050科幻大成真 超能力 心智控制 人造記憶 遺忘藥丸 奈米機器人 即將改變我們的世界 博客來 187 2018 12 23 原始内容存档于2021 01 25 國外的一些研究機構來告訴你 毒品是怎么樣毀掉你一生的 9900 新聞頻道 9900 台灣網站導航 2018 12 23 原始内容存档于2021 08 09 Vassoler FM Sadri Vakili G Mechanisms of transgenerational inheritance of addictive like behaviors Neuroscience 2014 264 198 206 PMC 3872494 PMID 23920159 doi 10 1016 j neuroscience 2013 07 064 The environment also plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time UNODC 2012 Therefore both genetics and the environment contribute to an individual s vulnerability to become addicted following an initial exposure to drugs of abuse Slade T Johnston A Teesson M Whiteford H Burgess P Pirkis J Saw S The Mental Health of Australians 2 Substance Use Disorders in Australia PDF Department of Health and Ageing Canberra May 2009 2017 05 02 原始内容存档 PDF 于2020 08 18 外部連結 编辑台灣成癮科學學會 页面存档备份 存于互联网档案馆 取自 https zh wikipedia org w index php title 成瘾 amp oldid 74943492, 维基百科，wiki，书籍，书籍，图书馆，
