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[15]
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[22]
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?? ?????? ???????? ????????? ???????? ?????? ???????. ??? CREB ?? ?????? ??????? ?? ??? ??
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[23]
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- ^
?????? ????? ????
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??????? ?? FOS ???????? ?????? ??Δ????? ????
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?? ?????? ???????? ???? ???? ????? ??? ???????? ?? ??? ??????.
[8]
??? ????? FOS? ???? ????? ???????? Fos ? (Fos
?FOSL1
?FOSL2
?FOSB
?Δ?????) ????? ???? ???? ?? ????? ????? ?? ??????? ?? Δ?????.
[8]
- ^
???? ????????? ??????? ???? ????? ?? ??? ?? ?????? ?? ????? ?????? ??????? ?? ?????????? ?? ?????? ???????
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??? ???? ?????? ??? ?????? ??? ????????.
- ^
?????? ???????? ?? "?????? ????????" ??????? ?? ??? "
??????
" ?? "
????????
" ???? ????? ????? ????? ??????? ?????? ?????? ???????.
[15]
[16]
?????? ???? ???? ?????? ?????? "????????" ?????? ???? ???????? ???? ????? ?????? ?????? ?????? ????.
[15]
- ^
?????? ????? ???? ??? ??? ??? ??????? ?????? ????? ?? ??????????? ???? ?????? ?? ?????? ??? ???? ????????? ??? ??? ??????? ???? ?? ????? ????.
?????
[
???
]
- ^
"Facing Addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health"
(PDF)
.
Office of the Surgeon General
. US Department of Health and Human Services. ?????? 2016. ?. 35?37, 45, 63, 155, 317, 338. ????? ??
?????
(PDF)
?? 2020-02-09
. ???? ???? ??????
2017-01-28
.
- ^
Angres DH? Bettinardi-Angres K (?????? 2008). "The disease of addiction: origins, treatment, and recovery".
Disease-a-Month
. ?. 54 ?. 10: 696?721.
DOI
:
10.1016/j.disamonth.2008.07.002
.
PMID
:
18790142
.
- ^
[2]
- ^
American Society for Addiction Medicine (2012).
"Definition of Addiction"
. ????? ??
?????
?? 2019-12-13.
- ^
?
?
?
?
Ruffle JK (?????? 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?".
Am. J. Drug Alcohol Abuse
. ?. 40 ?. 6: 428?37.
DOI
:
10.3109/00952990.2014.933840
.
PMID
:
25083822
.
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.
- ^
?
?
?
?
?
?
?
?
?
?
??
??
??
??
??
Olsen CM (?????? 2011).
"Natural rewards, neuroplasticity, and non-drug addictions"
.
Neuropharmacology
. ?. 61 ?. 7: 1109?22.
DOI
:
10.1016/j.neuropharm.2011.03.010
.
PMC
:
3139704
.
PMID
:
21459101
.
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
"
- ^
Malenka RC? Nestler EJ? Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders".
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
(?. 2nd). New York: McGraw-Hill Medical. ?. 364?375.
ISBN
:
9780071481274
.
- ^
?
?
?
?
?
Nestler EJ (?????? 2013).
"Cellular basis of memory for addiction"
.
Dialogues Clin. Neurosci
. ?. 15 ?. 4: 431?443.
PMC
:
3898681
.
PMID
:
24459410
.
Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.
41
. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
- ^
"Glossary of Terms"
.
Mount Sinai School of Medicine
. Department of Neuroscience
. ???? ???? ??????
2015-02-09
.
- ^
Volkow ND? Koob GF? McLellan AT (????? 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction".
N. Engl. J. Med
. ?. 374 ?. 4: 363?371.
DOI
:
10.1056/NEJMra1511480
.
PMID
:
26816013
.
Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.
- ^
???? ???????? ????????? ???????? ??????? ?????????
???? ??????
2011-10-20 ??
Wayback Machine
[
???? ??????
]
- ^
?
?
the war on drugs
? .
???? ??????
2018-06-08 ??
Wayback Machine
- ^
Drug War Statistics
? .
???? ??????
2017-07-05 ??
Wayback Machine
- ^
?
?
?
Nestler EJ (?????? 2008).
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Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch ? from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure ? cited earlier (Renthal et al. in press). The mechanism responsible for ΔFosB repression of c-fos expression is complex and is covered below. ...
Examples of validated targets for ΔFosB in nucleus accumbens ... GluR2 ... dynorphin ... Cdk5 ... NFκB ... c-Fos
Table 3
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?
?
?
?
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???? ????? ?????? ??? ?????? ?????
<ref>
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Levy2019
- ^
???? ????? ?????? ??? ?????? ?????
<ref>
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??????
G9a reverses ΔFosB plasticity
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?
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<ref>
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Amph-Sex X-sensitization through D1 signaling
- ^
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<ref>
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Amph-Sex X-sensitization through NMDA signaling
- ^
???? ????? ?????? ??? ?????? ?????
<ref>
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pmid11572966
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