Substance abuse, or drug abuse, happens when a person uses a drug over and over again, in ways that hurt their health. The person is using the drug to change his or her mood or to feel better, not for any healthy reason. Sometimes when the person uses the drug for a long time, they will start to act differently. Some of the drugs are illegal to have or use, or can have certain limits that the person does not follow. Someone who thinks that they need a drug is called an addict.
Is it substance abuse?[change | change source]
Substance abuse can have different symptoms in different people. “Drug abuse” is not used in the DSM or ICD. In the DSM, the term “substance abuse” is used instead to mean the misuse of one of ten different types of drugs. A person can also become dependent on drugs. Repetitive use of a drug can cause dependence as well as tolerance. Tolerance happens when it takes more of a drug to produce the same effect than a previous time.
The term “drug misuse” is sometimes used when the drug being used is a prescription medication that are classified as sedatives (medicines that make someone calm), anxiolytics (medicines that make someone less worried or anxious), analgesics (medicines that reduce pain), or stimulants (medicines that give someone more energy). Someone who abuses there drugs may have to illegally buy them from someone who gets them from a doctor.
Not everyone agrees on the definition of substance abuse. Different countries have different rules for what is a drug and what drugs are illegal. People also do not agree about what is abuse. In most Western countries, one glass of wine is acceptable, but drinking more than one bottle at once is abuse. To some people, any drinking can be seen as abuse. In the United States, any use of marijuana is illegal, except in a few states where marijuana can be given by a doctor.
What causes people to abuse substances?[change | change source]
In many cases, when a person is using drugs, their thinking and behaviors change. Sometimes, they commit crimes while using drugs. They may do things that are not safe, like drive a car while drunk. When people abuse drugs over a longer time, their personalities often change as well. The people who abuse drugs are often addicted. Since many of these drugs are illegal, very often drug abusers have problems with the law.
There are two major ideas about why people abuse drugs. One is that a person’s genes cause them to be likely to become dependent on drugs. In this case, the drug abuse is learned from someone else, usually a family member or friend. The other major idea is that drug use is a habit that becomes harmful. In this case, if a person becomes addicted, they begin to abuse the drug.
What kind of drugs are abused?[change | change source]
People abuse drugs in many different ways, including:
Illegal drugs[change | change source]
Some of the most commonly abused illegal drugs are:
Legal drugs and medicines[change | change source]
Some of the most commonly abused legal drugs and medicines are:
Substance abuse, depression, and suicide[change | change source]
People who abuse drugs have a high rate of suicide. This is because of the changes in the brain caused by drugs, both when they are being used and the changes they cause over time. Another cause is the loss of family and friends because of the drug abuse. In the United States, about 30% of all people who perform suicide have abused alcohol at some point.
This table explains more about how some commonly abused drugs relate to depression and suicide:
|Substance abused||Effects related to suicide|
|Alcohol||People who misuse alcohol are more likely to have a number of mental health disorders. Alcoholics have a very high suicide rate. Suicide from alcoholism is more common in older adults. If a person drinks 6 or more drinks per day, they are six times more likely to commit suicide. Many heavy drinkers have major depressive disorder, and heavy drinking itself can cause major depressive disorder in a lot of alcoholics.|
|Benzodiazepines||People are more likely to be depressed, and have a higher risk of suicide, if they have been abusing benzodiazepines (like Xanax) or using them for a long time. Depressed adolescents who were taking benzodiazepines were much more likely to hurt themselves or kill themselves.|
|Cigarettesmoking||Many studies have shown a link between smoking, thinking about suicide, and suicide attempts. In studies done with 50,000 nurses and 300,000 male U.S. Armysoldiers, the people who smoked between 1 to 24 cigarettes per day had twice the suicide risk, and people who smoked 25 cigarettes or more had 4 times the suicide risk, as compared with those who had never smoked.|
|Cocaine||Misuse of drugs such as cocaine often has a link with suicide. When cocaine's effects wear off, people go through cocaine withdrawal. During this time, many people feel very bad. Suicide is most likely to happen during this time in people who use a lot of cocaine or are addicted. In younger adults, suicide more commonly happens when two or more drugs are taken together.|
|Crystal meth||Crystal meth use has a strong link with depression and suicide, as well as a range of other bad effects on physical and mental health.|
|Heroin||3% to 35% of deaths among heroin users are thought to be from suicide. Overall, heroin users are 14 times more likely than people who do not use heroin to die from suicide.|
Treating substance abuse[change | change source]
Treatment of substance abuse can include both therapy and medicine. Therapy for substance abuse helps people not use drugs when they feel they need to. For children and young adults, both the child and the family may have therapy. The child will learn how to not abuse, and the family will learn how to help the child. The organization Alcoholics Anonymous helps people with alcohol abuse.
For some kinds of substance abuse, medicine can be used to help. Some of these medicines, such as methadone, stop the drug from working in the brain. Other medicines can cause people to feel ill if they use the substance that they abuse.
Many substances can cause withdrawal. Withdrawal is a group of things that happen when someone who regularly takes a drug stops using that drug. For someone to have withdrawal, they must be addicted to the drug. Different drugs cause different things to happen during withdrawal. They can also cause different amounts of trouble for the person in withdrawal. Withdrawal for some drugs, like heroin and other opiates, can be dangerous and should be done with someone taking care of the person in withdrawal.
Likelihood[change | change source]
About 9% of Americans have a substance abuse issue. Young people are the most likely to experiment with and abuse drugs. Drug abuse affects about 5% of adolescents. More men than women have substance abuse disorder, though women are more likely to have an issue with abusing prescription medication. Children who have parents with substance abuse issues are more likely to have a substance abuse issue when they grow up.
Special populations[change | change source]
Certain groups of people are more likely to develop substance abuse issues. One group is immigrants or other people who have left their home country. They often have issues in their new country, and some use drugs as a way to feel better. Another group that is at risk is homeless children. They will use drugs to become closer to each other. A third group that is at risk is musicians. They may use stimulants to make themselves more active and happy. Singers can also hurt themselves if they use drugs that are inhaled.
History[change | change source]
The first official definition for substance abuse was made in 1932 by the American Psychiatric Association. This definition was only used for when the substance was illegal and not being used as medicine. In 1966, the American Medical Association defined abuse as the drug being given by someone to themselves without a doctor.
The first edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) had drug abuse as a symptom of other psychological issues. In the third edition, substance abuse was made its own issue. The DSM also has drug abuse as a different issue than drug dependence, which is defined as compulsive use of a drug.
Society and culture[change | change source]
Most countries have laws that make having or using certain drugs illegal. The rules for these drugs can be different between countries or in different parts of the same country. Many drugs that are illegal in several places are sold to make money for groups known as drug cartels.
Drug abuse can also cause issues in a country’s economy. According to the European Union, about 2.5 billion dollars are lost each year because of people abusing drugs. This loss comes from people not going to work or having to go to the hospital because of side effects of the drug. In the United Kingdom, about 29 billion dollars a year are lost. This number does not include the cost of police or other law enforcement. In the United States, the cost was 181 billion dollars in 2002. This number includes costs because of health issues, loss of work, law enforcement, and welfare programs.
Related pages[change | change source]
References[change | change source]
- ↑American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
- ↑Barrett SP, Meisner JR, Stewart SH (November 2008). "What constitutes prescription drug misuse? Problems and pitfalls of current conceptualizations" (PDF). Curr Drug Abuse Rev 1 (3): 255–62.
- ↑"Addiction is a Chronic Disease". http://archives.drugabuse.gov/about/welcome/aboutdrugabuse/chronicdisease.
- ↑ 4.04.1"Commonly Abused drugs Charts". DrugAbuse.gov. National Institute on Drug Abuse. October 2015. Retrieved December 24, 2015.
- ↑Isralowitz, Richard (2004). Drug use: a reference handbook. Santa Barbara, Calif.: ABC-CLIO. pp. 122–123. ISBN 978-1-57607-708-5.
- ↑Chignon JM, Cortes MJ, Martin P, Chabannes JP (July 1998). "[Attempted suicide and alcohol dependence: results of an epidemiologic survey]" (in French). Encephale24 (4): 347–54. PMID 9809240.
- ↑O'Donohue, William T.; R. Byrd, Michelle; Cummings, Nicholas A.; Henderson, Deborah P. (2005). Behavioral integrative care: treatments that work in the primary care setting. New York: Brunner-Routledge. p. 115. ISBN 978-0-415-94946-0.
- ↑Ayd, Frank J (31 May 2000). Lexicon of psychiatry, neurology, and the neurosciences. Philadelphia: Lippincott-Williams Wilkins. p. 256. ISBN 978-0-7817-2468-5.
- ↑Fergusson DM, Boden JM, Horwood LJ (March 2009). "Tests of causal links between alcohol abuse or dependence and major depression". Arch. Gen. Psychiatry66 (3): 260–6. doi:10.1001/archgenpsychiatry.2008.543. PMID 19255375. http://archpsyc.ama-assn.org/cgi/pmidlookup?view=long&pmid=19255375.
- ↑Taiminen TJ (January 1993). "Effect of psychopharmacotherapy on suicide risk in psychiatric inpatients". Acta Psychiatr Scand87 (1): 45–7. doi:10.1111/j.1600-0447.1993.tb03328.x. PMID 8093823.
- ↑Brent DA, Emslie GJ, Clarke GN et al. (April 2009). "Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study". Am J Psychiatry166 (4): 418–26. doi:10.1176/appi.ajp.2008.08070976. PMID 19223438. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=19223438.
- ↑Iwasaki M, Akechi T, Uchitomi Y, Tsugane S (April 2005). "Cigarette Smoking and Completed Suicide among Middle-aged Men: A Population-based Cohort Study in Japan". Annals of Epidemiology15 (4): 286–92. doi:10.1016/j.annepidem.2004.08.011. PMID 15780776.
- ↑Miller M, Hemenway D, Rimm E (May 2000). "Cigarettes and suicide: a prospective study of 50,000 men". American journal of public health90 (5): 768–73. doi:10.2105/AJPH.90.5.768. PMC 1446219. PMID 10800427.
- ↑Hemenway D, Solnick SJ, Colditz GA (February 1993). "Smoking and suicide among nurses". American journal of public health83 (2): 249–51. doi:10.2105/AJPH.83.2.249. PMC 1694571. PMID 8427332.
- ↑Miller M, Hemenway D, Bell NS, Yore MM, Amoroso PJ (June 2000). "Cigarette smoking and suicide: a prospective study of 300,000 male active-duty Army soldiers". American Journal of Epidemiology151 (11): 1060–3. PMID 10873129.
- ↑Darke, S.; Kaye, S.; McKetin, R.; Duflou, J. (May 2008). "Major physical and psychological harms of methamphetamine use". Drug Alcohol Rev27 (3): 253–62. doi:10.1080/09595230801923702. PMID 18368606.
- ↑Darke S, Ross J (November 2002). "Suicide among heroin users: rates, risk factors and methods". Addiction97 (11): 1383–94. doi:10.1046/j.1360-0443.2002.00214.x. PMID 12410779. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0965-2140&date=2002&volume=97&issue=11&spage=1383.
- ↑"Self-Help Groups Article". Retrieved May 27, 2015
- ↑The California Evidence-Based Clearinghouse: Current Pharmacological Treatment Available for Alchhol Abuse. Copyright 2006-2013.
- ↑National Institute on Alcohol Abuse and Alcoholism. (2005). Module 10F: Immigrants, refugees, and alcohol. In NIAAA: Social work education for the prevention and treatment of alcohol use disorders (NIH publication). Washington, D.C.
- ↑Cottrell-Boyce, Joe (2010). "THE ROLE OF SOLVENTS IN THE LIVES OF STREET CHILDREN" (PDF). African Journal of Drug & Alcohol Studies 9 (2): 93–102. doi:10.4314/ajdas.v9i2.64142. Retrieved 28 January 2014.
- ↑Breitenfeld D., Thaller V., Perić B., Jagetic N., Hadžić D., Breitenfeld T. (2008). "Substance abuse in performing musicians". Alcoholism: Journal on Alcoholism and Related Addictions 44 (1): 37–42.
- ↑Glasscote, R.M., Sussex, J.N., Jaffe, J.H., Ball, J., Brill, L. (1932). The Treatment of Drug Abuse for people like you...: Programs, Problems, Prospects. Washington, D.C.: Joint Information Service of the American Psychiatric Association and the National Association for Mental Health.
"Addictive" redirects here. For other uses, see Addiction (disambiguation) and Addictive (disambiguation).
|Addiction and dependence glossary|
Addiction is a brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences. Despite the involvement of a number of psychosocial factors, a biological process – one which is induced by repeated exposure to an addictive stimulus – is the core pathology that drives the development and maintenance of an addiction. The two properties that characterize all addictive stimuli are that they are reinforcing (i.e., they increase the likelihood that a person will seek repeated exposure to them) and intrinsically rewarding (i.e., they are perceived as being inherently positive, desirable, and pleasurable).
Addiction is a disorder of the brain's reward system which arises through transcriptional and epigenetic mechanisms and occurs over time from chronically high levels of exposure to an addictive stimulus (e.g., eating food, the use of cocaine, engagement in sexual intercourse, participation in high-thrill cultural activities such as gambling, etc.).ΔFosB, a gene transcription factor, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions. Two decades of research into ΔFosB's role in addiction have demonstrated that addiction arises, and the associated compulsive behavior intensifies or attenuates, along with the overexpression of ΔFosB in the D1-typemedium spiny neurons of the nucleus accumbens. Due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction biomarker. ΔFosB expression in these neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement, while decreasing sensitivity to aversion.[note 1]
As described by two groups of researchers, addiction exacts an "astoundingly high financial and human toll" on individuals and society as a whole through the direct adverse effects of drugs, associated healthcare costs, long-term complications (e.g., lung cancer with smoking tobacco, liver cirrhosis with drinking alcohol, or meth mouth from intravenous methamphetamine), the functional consequences of altered neural plasticity in the brain, and the consequent loss of productivity. Classic hallmarks of addiction include impaired control over substances or behavior, preoccupation with substance or behavior, and continued use despite consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs).
Examples of drug and behavioral addictions include: alcoholism, amphetamine addiction, cocaine addiction, nicotine addiction, opiate addiction, food addiction, gambling addiction, and sexual addiction. The only behavioral addiction recognized by the DSM-5 and the ICD-10 is gambling addiction. The term addiction is misused frequently to refer to other compulsive behaviors or disorders, particularly dependence, in news media. An important distinction between drug addiction and dependence is that drug dependence is a disorder in which cessation of drug use results in an unpleasant state of withdrawal, which can lead to further drug use. Addiction is the compulsive use of a substance or performance of a behavior that is independent of withdrawal.
This section needs expansion. You can help by adding to it.(February 2016)
Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite processes (i.e., internal vs external or environmental, respectively) that compete over the control of an individual's elicited behaviors. Cognitive control, and particularly inhibitory control over behavior, is impaired in both addiction and attention deficit hyperactivity disorder. Stimulus-driven behavioral responses (i.e., stimulus control) that are associated with a particular rewarding stimulus tend to dominate one's behavior in an addiction.
Stimulus control of behavior
See also: Stimulus control
Cognitive control of behavior
See also: Cognitive control
Main article: Behavioral addiction
The term behavioral addiction correctly refers to a compulsion to engage in a natural reward – which is a behavior that is inherently rewarding (i.e., desirable or appealing) – despite adverse consequences. Preclinical evidence has demonstrated that marked increases in the expression of ΔFosB through repetitive and excessive exposure to a natural reward induces the same behavioral effects and neuroplasticity as occurs in a drug addiction.
Reviews of both clinical research in humans and preclinical studies involving ΔFosB have identified compulsive sexual activity – specifically, any form of sexual intercourse – as an addiction (i.e., sexual addiction). Moreover, reward cross-sensitization between amphetamine and sexual activity, meaning that exposure to one increases the desire for both, has been shown to occur preclinically and clinically as a dopamine dysregulation syndrome; ΔFosB expression is required for this cross-sensitization effect, which intensifies with the level of ΔFosB expression.
Reviews of preclinical studies indicate that long-term frequent and excessive consumption of high fat or sugar foods can produce an addiction (food addiction).
Gambling is a natural reward which is associated with compulsive behavior and for which clinical diagnostic manuals, namely the DSM-5, have identified diagnostic criteria for an "addiction". There is evidence from functional neuroimaging that gambling activates the reward system and the mesolimbic pathway in particular. Similarly, shopping and playing videogames are associated with compulsive behaviors in humans and have also been shown to activate the mesolimbic pathway and other parts of the reward system. Based upon this evidence, gambling addiction, video game addiction and shopping addiction are classified accordingly.
There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Roughly half of an individual's risk for developing an addiction is derived from genetics, while the other half is derived from the environment. However, even in individuals with a relatively low genetic loading, exposure to sufficiently high doses of an addictive drug for a long period of time (e.g., weeks–months) can result in an addiction. In other words, anyone can become an addict under the right circumstances.
It has long been established that genetic factors along with environmental (e.g., psychosocial) factors are significant contributors to addiction vulnerability. Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug addiction have been indicated by other studies. Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to addiction in several ways. For example, altered levels of a normal protein due to environmental factors could then change the structure or functioning of specific brain neurons during development. These altered brain neurons could change the susceptibility of an individual to an initial drug use experience. In support of this hypothesis, animal studies have shown that environmental factors such as stress can affect an animal's genotype.
Overall, the data implicating specific genes in the development of drug addiction is mixed for most genes. One reason for this may be that the case is due to a focus of current research on common variants. Many addiction studies focus on common variants with an allele frequency of greater than 5% in the general population, however when associated with disease, these only confer a small amount of additional risk with an odds ratio of 1.1–1.3 percent. On the other hand, the rare variant hypothesis states that genes with low frequencies in the population (<1%) confer much greater additional risk in the development of disease.
Genome-wide association studies (GWAS) are a recently developed research method which are used to examine genetic associations with dependence, addiction, and drug use. These studies employ an unbiased approach to finding genetic associations with specific phenotypes and give equal weight to all regions of DNA, including those with no ostensible relationship to drug metabolism or response. These studies rarely identify genes from proteins previously described via animal knockout models and candidate gene analysis. Instead, large percentages of genes involved in processes such as cell adhesion are commonly identified. This is not to say that previous findings, or the GWAS findings, are erroneous. The important effects of endophenotypes are typically not capable of being captured by these methods. Furthermore, genes identified in GWAS for drug addiction may be involved either in adjusting brain behavior prior to drug experiences, subsequent to them, or both. 
A study that highlights the significant role genetics play in addiction is the twin studies. Twins have similar and sometimes identical genetics. Analyzing these genes in relation to genetics has helped geneticists understand how much of a role genes play in addiction. Studies performed on twins found that rarely did only one twin have an addiction. In most cases where at least one twin suffered from an addiction, both did, and often to the same substance.
Environmental risk factors for addiction are the experiences of an individual during their lifetime that interact with the individual's genetic composition to increase or decrease the his or her vulnerability to addiction. A number of different environmental factors have been implicated as risk factors for addiction, including various psychosocial stressors; however, an individual's exposure to an addictive drug is by far the most significant environmental risk factor for addiction. The National Institute on Drug Abuse cites lack of parental supervision, the prevalence of peer substance use, drug availability, and poverty as risk factors for substance use among children and adolescents.
Adverse childhood experiences (ACEs) are various forms of maltreatment and household dysfunction experienced in childhood. The Adverse Childhood Experiences Study by the Centers for Disease Control and Prevention has shown a strong dose–response relationship between ACEs and numerous health, social, and behavioral problems throughout a person's lifespan, including those associated with substance abuse. Children's neurological development can be permanently disrupted when they are chronically exposed to stressful events such as physical, emotional, or sexual abuse, physical or emotional neglect, witnessing violence in the household, or a parent being incarcerated or suffering from a mental illness. As a result, the child's cognitive functioning or ability to cope with negative or disruptive emotions may be impaired. Over time, the child may adopt substance use as a coping mechanism, particularly during adolescence. A study of 900 court cases involving children who experienced abuse found that a vast amount of them went on to suffer from some form of addiction in their adolescence or adult life. This pathway towards addiction that is opened through stressful experiences during childhood can be avoided by a change in environmental factors throughout an individuals life and opportunities of professional help.
Adolescence represents a period of unique vulnerability for developing addiction. In adolescence, the incentive–rewards systems in the brain mature well before the cognitive control center. This consequentially grants the incentive–rewards systems a disproportionate amount of power in the behavioral decision making process. Therefore, adolescents are increasingly likely to act on their impulses and engage in risky, potentially addicting behavior before considering the consequences. Not only are adolescents more likely to initiate and maintain drug use, but once addicted they are more resistant to treatment and more liable to relapse. Statistics have shown that those who start to drink alcohol at a younger age are more likely to become dependent later on. About 33% of the population tasted their first alcohol between the ages of 15 and 17, while 18% experienced it prior to this. As for alcohol abuse or dependence, the numbers start off high with those who first drank before they were 12 and then drop off after that. For example, 16% of alcoholics began drinking prior to turning 12 years old, while only 9% first touched alcohol between 15 and 17. This percentage is even lower, at 2.6%, for those who first started the habit after they were 21.
Most individuals are exposed to and use addictive drugs for the first time during their teenage years. In the United States, there were just over 2.8 million new users of illicit drugs in 2013, or about 7,800 new users per day. Over half (54.1 percent) were under 18 years of age.
Individuals with comorbid (i.e., co-occurring) mental health disorders such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD) or post-traumatic stress disorder are more likely to develop substance use disorders. The National Institute on Drug Abuse cites early aggressive behavior as a risk factor for substance use.
Transgenerational epigenetic factors
See also: Transgenerational epigenetic inheritance
Epigenetic genes and their products (e.g., proteins) are the key components through which environmental influences can affect the genes of an individual; they also serve as the mechanism responsible for the transgenerational epigenetic inheritance of behavioral phenotypes, a phenomenon in which environmental influences on the genes of a parent can affect the associated traits and behavioral phenotypes of their offspring (e.g., behavioral responses to certain environmental stimuli). In addiction, epigenetic mechanisms play a central role in the pathophysiology of the disease; it has been noted that some of the alterations to the epigenome which arise through chronic exposure to addictive stimuli during an addiction can be transmitted across generations, in turn affecting the behavior of one's children (e.g., the child's behavioral responses to addictive drugs and natural rewards). More research is needed to determine the specific epigenetic mechanisms and the nature of heritable behavioral phenotypes that arise from addictions in humans. Based upon preclinical evidence with lab animals, the addiction-related behavioral phenotypes that are transmitted across generations may serve to increase or decrease the child's risk of developing an addiction.
|Transcription factor glossary|
Signaling cascade in the nucleus accumbens that results in psychostimulant addiction
This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine. Following presynaptic dopamine and glutamateco-release by such psychostimulants,postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP-dependent pathway and a calcium-dependent pathway that ultimately result in increased CREB phosphorylation. Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fos gene with the help of corepressors;c-Fosrepression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron. A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for 1–2 months, slowly accumulates following repeated high-dose exposure to stimulants through this process. ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.
Chronic addictive drug use causes alterations in gene expression in the mesocorticolimbic projection. The most important transcription factors that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NF-κB). ΔFosB is the most significant biomolecular mechanism in addiction because the overexpression of ΔFosB in the D1-typemedium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and behavioral effects (e.g., expression-dependent increases in drug self-administration and reward sensitization) seen in drug addiction. ΔFosB expression in nucleus accumbensD1-typemedium spiny neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement while decreasing sensitivity to aversion.[note 1] Specific drug addictions in which ΔFosB has been implicated in addictions to alcohol, amphetamine, cannabinoids, cocaine, methylphenidate, nicotine, phenylcyclidine, propofol, opiates, and substituted amphetamines, among others.ΔJunD, a transcription factor, and G9a, a histone methyltransferase, both oppose the function of ΔFosB and inhibit increases in its expression. Increases in nucleus accumbens ΔJunD expression (via viral vector-mediated gene transfer) or G9a expression (via pharmacological means) reduces, or with a large increase can even block, many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).
ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Natural rewards, like drugs of abuse, induce gene expression of ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression. Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards (i.e., behavioral addictions) as well; in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward. Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess bidirectional cross-sensitization effects that are mediated through ΔFosB. This phenomenon is notable since, in humans, a dopamine dysregulation syndrome, characterized by drug-induced compulsive engagement in natural rewards (specifically, sexual activity, shopping, and gambling), has also been observed in some individuals taking dopaminergic medications.
ΔFosB inhibitors (drugs or treatments that oppose its action) may be an effective treatment for addiction and addictive disorders.
The release of dopamine in the nucleus accumbens plays a role in the reinforcing qualities of many forms of stimuli, including naturally reinforcing stimuli like palatable food and sex. Altered dopamine neurotransmission is frequently observed following the development of an addictive state. In humans and lab animals that have developed an addiction, alterations in dopamine or opioid neurotransmission in the nucleus accumbens and other parts of the striatum are evident. Studies have found that use of certain drugs (e.g., cocaine) affect cholinergic neurons that innervate the reward system, in turn affecting dopamine signaling in this region.
Summary of addiction-related plasticity
Main article: Reward system
This section needs expansion. You can help by adding to it.(August 2015)
Understanding the pathways in which drugs act and how drugs can alter those pathways is key when examining the biological basis of drug addiction. The reward pathway, known as the mesolimbic pathway, or its extension, the mesocorticolimbic pathway, is characterized by the interaction of several areas of the brain.
- The projections from the ventral tegmental area (VTA) are a network of dopaminergicneurons with co-localized postsynaptic glutamate receptors (AMPAR and NMDAR). These cells respond when stimuli indicative of a reward are present. The VTA supports learning and sensitization development and releases DA into the forebrain. These neurons also project and release DA into the nucleus accumbens, through the mesolimbic pathway. Virtually all drugs causing drug addiction increase the dopamine release in the mesolimbic pathway, in addition to their specific effects.
- The nucleus accumbens (NAcc) is one output of the VTA projections. The nucleus accumbens itself consists mainly of GABAergicmedium spiny neurons (MSNs). The NAcc is associated with acquiring and eliciting conditioned behaviors, and is involved in the increased sensitivity to drugs as addiction progresses. Overexpression of ΔFosB in the nucleus accumbens is a necessary common factor in essentially all known forms of addiction; ΔFosB is a strong positive modulator of positively reinforced behaviors.
- The prefrontal cortex, including the anterior cingulate and orbitofrontal cortices, is another VTA output in the mesocorticolimbic pathway; it is important for the integration of information which helps determine whether a behavior will be elicited. It is also critical for forming associations between the rewarding experience of drug use and cues in the environment. Importantly, these cues are strong mediators of drug-seeking behavior and can trigger relapse even after months or years of abstinence.
Other brain structures that are involved in addiction include:
- The basolateral amygdala projects into the NAcc and is thought to also be important for motivation.
- The hippocampus is involved in drug addiction, because of its role in learning and memory. Much of this evidence stems from investigations showing that manipulating cells in the hippocampus alters dopamine levels in NAcc and firing rates of VTA dopaminergic cells.
Role of dopamine and glutamate
Dopamine is the primary neurotransmitter of the reward system in the brain. It plays a role in regulating movement, emotion, cognition, motivation, and feelings of pleasure. Natural rewards, like eating, as well as recreational drug use cause a release of dopamine, and are associated with the reinforcing nature of these stimuli. Nearly all addictive drugs, directly or indirectly, act upon the brain's reward system by heightening dopaminergic activity.
Excessive intake of many types of addictive drugs results in repeated release of high amounts of dopamine, which in turn affects the reward pathway directly through heightened dopamine receptor activation. Prolonged and abnormally high levels of dopamine in the synaptic cleft can induce receptor downregulation in the neural pathway. Downregulation of mesolimbic dopamine receptors can result in a decrease in the sensitivity to natural reinforcers.
Drug seeking behavior is induced by glutamatergic projections from the prefrontal cortex to the nucleus accumbens. This idea is supported with data from experiments showing that drug seeking behavior can be prevented following the inhibition of AMPA glutamate receptors and glutamate release in the nucleus accumbens.
|Neural effects||Behavioral effects|
|c-Fos||↓||Molecular switch enabling the chronic|
induction of ΔFosB[note 2]