Malenka RC, Nestler EJ, Hyman SE. Chapter 15: Reinforcement and Addictive Disorders. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 364–368. ISBN 9780071481274. The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences. ... Addictive drugs are both rewarding and reinforcing. ... Familiar pharmacologic terms such as tolerance, dependence, and sensitization are useful in describing some of the time-dependent processes that underlie addiction. ... Dependence is defined as an adaptive state that develops in response to repeated drug administration, and is unmasked during withdrawal, which occurs when drug taking stops. Dependence from long-term drug use may have both a somatic component, manifested by physical symptoms, and an emotional–motivation component, manifested by dysphoria. While physical dependence and withdrawal occur with some drugs of abuse (opiates, ethanol), these phenomena are not useful in the diagnosis of addiction because they do not occur with other drugs of abuse (cocaine, amphetamine) and can occur with many drugs that are not abused (propranolol, clonidine).
The official diagnosis of drug addiction by the Diagnostic and Statistic Manual of Mental Disorders (2000), which makes distinctions between drug use, abuse, and substance dependence, is flawed. First, diagnosis of drug use versus abuse can be arbitrary and reflect cultural norms, not medical phenomena. Second, the term substance dependence implies that dependence is the primary pharmacologic phenomenon underlying addiction, which is likely not true, as tolerance, sensitization, and learning and memory also play central roles. It is ironic and unfortunate that the Manual avoids use of the term addiction, which provides the best description of the clinical syndrome.
Substance use disorder. Pubmed Health. National Institutes of Health. [2014-09-12]. （原始内容存档于2014-03-31）. Drug dependence means that a person needs a drug to function normally. Abruptly stopping the drug leads to withdrawal symptoms. Drug addiction is the compulsive use of a substance, despite its negative or dangerous effects
Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nature Reviews. Neuroscience. October 2011, 12 (11): 623–37. 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.
Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M. Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms. Journal of Psychoactive Drugs. 2012, 44 (1): 38–55. PMC 4040958. PMID 22641964. doi:10.1080/02791072.2012.662112. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.
Nestler EJ. Reflections on: "A general role for adaptations in G-Proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function". Brain Research. August 2016, 1645: 71–4. PMC 4927417. PMID 26740398. doi:10.1016/j.brainres.2015.12.039. These findings led us to hypothesize that a concerted upregulation of the cAMP pathway is a general mechanism of opiate tolerance and dependence. ... We thus extended our hypothesis to suggest that, particularly within brain reward regions such as NAc, cAMP pathway upregulation represents a common mechanism of reward tolerance and dependence shared by several classes of drugs of abuse. Research since that time, by many laboratories, has provided substantial support for these hypotheses. Specifically, opiates in several CNS regions including NAc, and cocaine more selectively in NAc induce expression of certain adenylyl cyclase isoforms and PKA subunits via the transcription factor, CREB, and these transcriptional adaptations serve a homeostatic function to oppose drug action. In certain brain regions, such as locus coeruleus, these adaptations mediate aspects of physical opiate dependence and withdrawal, whereas in NAc they mediate reward tolerance and dependence that drives increased drug self-administration.
Rasmussen K. The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal. Neuropsychopharmacology. December 1995, 13 (4): 295–300. PMID 8747753. doi:10.1016/0893-133X(95)00082-O.
Reynolds M, Mezey G, Chapman M, Wheeler M, Drummond C, Baldacchino A. Co-morbid post-traumatic stress disorder in a substance misusing clinical population. Drug and Alcohol Dependence. March 2005, 77 (3): 251–8. PMID 15734225. doi:10.1016/j.drugalcdep.2004.08.017.
Moggi F, Giovanoli A, Strik W, Moos BS, Moos RH. Substance use disorder treatment programs in Switzerland and the USA: Program characteristics and 1-year outcomes. Drug and Alcohol Dependence. January 2007, 86 (1): 75–83. PMID 16782286. doi:10.1016/j.drugalcdep.2006.05.017.
Trips Beyond Addiction （页面存档备份，存于互联网档案馆） | Living Hero Radio Show and Podcast special. With Dimitri Mobengo Mugianis, Bovenga Na Muduma, Clare S. Wilkins, Brad Burge, Tom Kingsley Brown, Susan Thesenga, Bruce K. Alexander, PhD ~ the voices of ex-addicts, researchers from The Multidisciplinary Association for Psychedelic Studies and Ibogaine/Iboga/Ayahuasca treatment providers sharing their experiences in breaking addiction with native medicines. January 2013
