Ch 9: Addiction Flashcards
abstinence syndrome
Condition characterized by unpleasant symptoms when an individual tries to cease drug use.
allele
Alternative form of a gene. Multiple alleles of a gene differ by one or more nucleotides in the gene’s DNA sequence and may code for proteins with slightly different amino acid sequences.
allostasis
Adaptive biological process in which an organism’s response to repeated threats or challenges results in long-lasting physiological or behavioral changes. This concept is distinguished from homeostasis, which refers to the tendency of an organism to maintain physiological or behavioral stability in the face of threats or challenges (i.e., to remain unchanged).
anhedonia
Difficulty or lack of the ability to experience pleasure. Such a state is characteristic of many depressed patients and may also occur during drug withdrawal in an addicted person.
anti-reward system
Neural system that is thought to be engaged during the transition from impulsive to compulsive drug use. This system is an important contributor to the negative mood state induced by withdrawal from abused drugs.
biopsychosocial model
Model of addiction that attempts to give a full account of addiction by incorporating biological, psychological, and sociological factors.
breaking point
The point at which an animal will no longer expend the effort required to receive the reward (e.g., in a drug self-administration paradigm).
comorbidity
Diagnosis of simultaneous but distinct disease processes in an individual, such as the propensity for drug abusers to be diagnosed with other psychiatric problems.
craving
Strong urge addicts feel, compelling them to take a drug.
Delta FosB
Member of the Fos family of transcription factors. This protein accumulates in some brain areas (nucleus accumbens, dorsal striatum) after repeated exposure to various drugs of abuse and is hypothesized to contribute to the development of an addicted state. accumulation of this lasts at least several weeks after last drug administration bc the protein has a long half-life
disease model
Model of addiction that treats addiction as a distinct medical disorder or disease; based largely on evidence of dysregulation of brain function in addiction and on the idea that such dysfunction is at least partly caused by repeated drug exposure (neuroadaptations)
drug detoxification
Process whereby an individual eliminates a drug from the body and goes through an abstinence syndrome.
drug priming
Delivery of a small dose of a drug by the experimenter for the purpose of eliciting drug-seeking behavior, typically in an animal whose drug self-administration responding was previously extinguished.
drug reward
A positively-motivating subjective response to a drug, often experienced by humans as a euphoric feeling or “high.”
electrical self-stimulation
A procedure whereby an animal self-administers a weak electrical shock to a specific brain area due to the reinforcing properties of the stimulation.
executive function
Collection of higher-order cognitive abilities including planning, organization, problem solving, mental flexibility, and valuation of incentives. The prefrontal cortex plays an important role in executive function.
Gateway Theory
Theory proposing that use of certain drugs of abuse, particularly during childhood or adolescence, increases the risk of progressing to other substances. For example, tobacco or alcohol have been proposed as gateways to marijuana use, and in turn marijuana has been proposed as a gateway to so-called “hard drugs” like cocaine or heroin.
Heritability
The relative contribution of genetics to the variability of a trait within a population; .3-.8 for substance use disorders
Impaired response inhibition and salience attribution (IRISA)
Theory of addiction that emphasizes prefrontal cortical deficits leading to difficulty in refraining from drug use (impaired response inhibition) and the development of an abnormal psychological state in which drugs have much greater motivational power than normal reinforcers (impaired salience attribution).
moral model
Model of addiction that treats addiction as a personal and moral problem; reason why the medical model exists (to reduce sense of guilt)
natural recovery
Recovery from drug addiction without the aid of treatment; generally have less severe substance use problems
neuroadaptation
Changes in brain functioning that attempt to compensate for the effects of repeated substance use.
opponent-process model
Model of addiction in which the initial positive response to a drug is followed by an opposing withdrawal response as the drug wears off; over time repeated presentations of the stimulus altered the opponent process by strengthening its magnitude, reducing its latency to onet, and increasing its duration
place conditioning
Pavlovian conditioning procedure used to test the rewarding effects of drugs in rats and mice; the animals are exposed to drugs in specific compartments of an apparatus–with animals later choosing to spend more time in the drug compartment later on
positive reinforcer
Something (e.g., an abused drug) that, when provided to an organism, increases the strength of the response that was used to obtain the item. In studies of addiction, the positive reinforcing quality of a drug is usually measured by means of a self-administration procedure.
progressive-ratio procedure
Method used to measure the relative power of drug reinforcement by steadily increasing the response to reward ratio. Eventually leads to the breakpoint
relapse
Recurrence of drug use following a period of abstinence.
remission
Period in which an addict is drug free.
reward circuit
Circuit of neurons that, when activated, mediates the rewarding effects of both natural rewards (e.g., food, water, sex) and drugs of abuse.
schedule of controlled substances
System established by the Controlled Substances Act in 1970 that classifies most substances with abuse potential into one of five schedules. Schedules I and II have the strictest guidelines.
self-medication hypothesis
Theory that addiction is based on an effort by the individual to treat oneself for mood or other ill feelings.
shared etiology
Situation in which multiple disorders are caused by the same set of factors. thus similiar things may lead to both addiction AND other psychiatric illness
substance abuse
Disorder involving the overuse of a drug by an individual. It may or may not lead to substance dependence.
substance dependence
Disorder involving excessive and harmful drug use by an individual, corresponding to addiction.
substance use disorder
New DSM-5 designation for a psychiatric disorder with features typically associated with addiction. This designation replaces both substance abuse and substance dependence categories in DSM-IV. A maladaptive pattern of substance use, over at least a 12 month period, that has led to significan impairment or distress by clinical standards
how many people are currently users of drugs?
22.5 million
Pure food and drug act
1906 regulated labeling of patent medicines and created the FDA
Harrison Act
1914 regulated the dispending and use of opioid drugs and cocaine
Eighteenth Constitutional Amendment
1920 prohibition; banned alcohol sales except for medicinal use
marijuana tax act
1937 banned nonmedical use of cannabis
controlled substances act
1970 established the schedule of controlled substances and created the DEA
physical dependence
abstinence from the drug leads to highly unpleasant withdrawal symptoms that motivate the individual to reinstate drug use
Definition of addiction
a behavioral pattern of drug use, characterized by overwhelming involvement with the use of a drug (compulsive use), the securing of its supply, and a high tendency to relapse after withdrawal
8 behaviors that are similiar to drug use
gambling, eating disorders, excessive internet use, preoccupation with love, preoccupation with sex excessive and compulsive exercising, workaholism, and compulsive shopping/spending
behavioral addictions
failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others
Two types of drug progression
- Gateway theory
- changes in the amount, pattern, and consequences of drug use as they affect the user’s health and functioning. May or may not progress to nonproblematic use
3 components of pathological drug use as a cyclical pattern
- periods of preoccupaiton with drugs and anticipation up upcoming use
- periods of drug intoxication that in some cases are associated with binging on the drug
- periods following drug use that are characterized by withdrawal symptoms and negative affect
maturing out
alcohol and marijuana use tend to naturally decrease as individuls enter adulthood and begin to take on adult responsibilities
schedule I substances
substances that have no accepted medical use and have a high abuse potential (heroin, LSD, mescaline, marijuana, MDMA)
Schedule II substances
substances that have a high abuse potential with severe psychotic or physical dependence liability (opium, morphine, codeine, amphetamine, ritalin, PCP)
schedule III substances
substances that have an abuse potential less than those in schedules I and II, including compounds containing limited quantities of certain narcotics and nonnarcotic drugs (barbiturates other than those in another schedule, paregoric)
Schedule IV drugs
substances that have an abuse potential less than those in schedule III (phenobarbital, valium, xanax)
schedule V drugs
substances that have an abuse potential less than those in schedule IV, consisting of preparations containing limited amounts of certain narcotic drugs generally for antitussive (cough suppressant) and antidiarrheal purposes
how do rates of administration relate to addiction?
routes that cause the fasted onset of drug action having the greatest addiction potential because they produce the strongest euhoric effects; However, fast onset is associated with a shorter duration of action
IV drug self-administration
substances that are strong reinforcers in the self-IV paradigm always have a great abuse liability in humans when taken intravenously or by smoking;
ways to effectively model relapse
- the experimenter delivering a small dose of the drug to the animal (drug priming)
- subjecting the animal to stress
- exposing the animal to environmental cues that were previously paired with drug delivery (prior to extinction)
why dont the negative consequences of addiction counteract the positive reinforcement?
possibly because drug induced euphoria occurs very quickly and the negative consequences occur later in time
can rewarding drugs be averisve?
YES! some substances can be reinforcing when self-administered by aversive when administered by an experimenter
physical dependence and continued drug use
some drugs lead to physical dependence, which causes unpleasant withdrawal symptoms when stopped. this can lead the user to take the drug again (relapse) to alleviate symptoms (negative reinforcement)
progression of drug taking behavior
impusive stage: primary motivation is the positive reinforcing effects
compulsive stage: primary motivation is the negative reinforcement of relief from withdrawal
what is a crucial symptom associated with conditioned withdrawal?
drug craving
what areas of the brain are activated by procuremen and use of evoked craving?
Increased: amygdala; anterior cingulate cortex
decreased: basal ganglia
what does drug seeking for relief from withdrawal fail to explain?
individuals who have gone through detox
factors that contribue to relapse
exposure to drug related stimuli, stress, boredom, lack of other reinforcers, desire to get high
internal states as cues
drugs can produce internal states that can serve as cues controlling the animal’s behavior in a learning task–> experienced users come to expect these subjective effects, and these expectations are thought to contribute to the persistence of drug-seeking/using behaviors
how many genes have been found to be addiction related?
1500
is genetic involvement of addiciton similiar across substances?
there is evidence for a common genetic involvement of 5 different molecular pathways across addictions to alcohol, nicotine, cocaine, opiate drugs
risk factors for abuse
younger age, less education, nonwhite ethnicity, lack of employment, stress and the person’s ability to cope with stress
what are addicts also typically diagnosed with?
anxiety, mood or personality disorders
three personality related pathways to addiction
- behavioral disinhibition: deviant behaviors (abuse) are linked to a trait cluster of impulsivity, antisociality, unconventionality, agressiveness, low levels of constraint and harm avoidance
- stress reduction: stress reactivity, anxiety, neuoticism–> vulnerability to stress
- reward sensitivity: sensation seeking, reward seeking, extraversion, gregariousness
Does it matter if your parent is an alcoholic?
children are at an increased risk for having alcohol or other substance abuse problems; may be related to modeling of the parent’s drinking behavior or to a heightened expectancy that drinking will lead to positive mood changes
4 functions served by drug abuse
- social facilitation
- remove the user from normal social roles and responsibilities
- promote group solidarity within a particular ethnic group
- drug subculture that embraces social rituals surrounding a particular subculture
what can reduce the risk of relapse?
moving to a new area, devloping new social relationships, obtaining employment, engaging in sbustitute activities like exercise or meditation
pathways in the reward circuit
mesolimbic and meocortical dopamine pathways; bed nucleus of the stria terminals; medial forebrain bundle; output pathway from the NAcc to the ventral pallidum
medial forebrain bundle
a collection of ascending and descending fibers that connects that ventral tegmental area with areas of the ventral forebrain including the nucleus accumbens, septal area, and olfactory tubercle
mesolimbic and meocortical dopamine pathways
that originate in the ventral tegmental area (VTA) of the midbrain and terminate in the nucleus accumbens (NAcc), amygdala (AMG), and frontal cortex (FC);
how do psychostimulants (cocaine/ amphetamine) exert their rewarding effects?
increasing transmission at the dopaminergic terminals in the nucleus accumbens.
how do opioid drugs and endogenous opioid peptides activate the reward circuit?
by stimulating opioid receptors in the ventral tegmental area, nucleus accumbens, amygdala
how does alcohol exert its effect?
enhances action of y-aminobutric acid (GABA) on GABAa receptors and this enhances DA release in the nucleus accumbens and opioid peptide release in the ventral tegmental area, nucleus accumbens, and the amygdala
what does nicotine activate?
the reward circuit by stimulating the nicotinic cholinergic receptors in the ventral tegmental area, nucleus accumbens, and amygdala; increases DA release
what does THC activate?
endogenous cannabinoids and THC stimulate cannabinoid receptors in the same brain areas; increase DA release
what plays a role in drug reward?
the mesolimbic DA pathway; the DA system is essential for drug reward only for some substances (cocaine/amphetamine) and not for others (heroine/ alcohol); opioid and cannabinoid systems are also involved
3 components of reward
- emotion/affect: subjective feelings of pleasure
- motivation: desire to obtain incentives
- learning/cognition: expectation that a particular action will lead to attainment of an incentive and strengthening of specific stimulus-response associations based on deliverty of the incentive
two types of neuroadaptations
- within-system
- between-system
within-system neuroadaptation
take place within the reward circuit and constitute a progressive down-regulation of activity in this circuit–> type of tolerance whereby the user experiences less pleasure from each episode of drug use
between system neuroadaptations
gradual recruitment of a neural circuit (anti-reward system) which leads to increased release of NE and two neuropeptides (corticotropin-releasing factor and dynorphin). This system puts a limit or brake on rewardand it mediates some of the averise effects of stress; plays a major role in the averise effects of withdrawal
brain changes after drug use that lead to addiction
transition from the nucleus accumbens to the dorsal striatum (caudate putament) as a key area for drug taking behavior–> this area is implicated in stimulus response habit learning which plays a significant role in the progression of drug taking from a reward-moticated behavior to a behavior that is automatic, habitual, and compulsive.
Disruptions of the glutamatergic pathway from the PFC to the nucleus accumbents–> impair the ability of the PFC to mediate response inhibition and impulse control
can drugs alter genes?
yes they can effect gene expression and proteins
transcription factors
proteins located in the cell nucleus that either stimulate or inhibit expression of a target gene (the rate of mRNA transcription) and accordingly up or down regulate levels of the protein encoded by the gene.
delta FosB overexpressing animals
show enhanced sensitivity to a variety of drug effects with the exception of morphine induced analegia
does delta FosB alter the brain?
yes–proteins regulated by delta FosB are involved in glutamate transmission and structural plasticity within the nuculeus accumbens
what may delta FosB play a major role in?
transition from controlled drug use to addiction
what does delta FosB do?
modulates gene and protein expression through epigenetic mechanisms
epigenetics
chromatin modifications that alter gene expression without changing the nucleotide sequence of the DNA strand
two types of epigenetic modifications
- methylation of the DNA at specific cytosines in the promoter region of the gene; promotes compaction of the chromatin (repressing gene expression)
- various modifications of the histone proteins that form complexes around which the DNA double helix is wrapped; facilitates gene expression by opening the chromatin and allowing transcriptional machinery to bing to DNA
most studied histone modification
acetylation–attachment of acetyl groups to specific sites along the tail of the protein
structural brain changes in addiction
in the prefrontal cortex (motivation; emotion regulation); executive function; reduced gray matter; volume reductions in the DLPFC, anterior cingulate cortex, orbitofrontal cortex; DA d2 receptor binding in the striatum is correlated with PFC glucose metabolism
three major PFC projections
- dorsolateral circuit that projects from the dorsolateral PFC to the dorsolateral caudate nucleus (executive function)
- ventromedial circuit–> connects anterior cingulate cortex with the nucleus accumbens (drive/motivation)
- orbitofrontal circuit–> orbitofrontal cortex to the ventromedial caudate (behavioral inhibition/ impulse control)
what is the amount of structual damage related to?
the severity / longevity of drug use
role of the striatum
cortical striatal loop: input from the midbrain DA neurons act on striatal D1 and D2 receptors to modulate striatal outflow and activity in the cortical striatal loops. Reduced D2 receptor levels may cause functional deficits (poor impulse control/ planning/ emotion regulation, abnormal salience attribution)
role of PFC and drug withdrawal
the ability of the dorsal PFC to exert behavioral control is diminished–> lead to a conflict over drug-taking behavior and increased vulnerability to taking more drugs. during repeated drug taking/ intoxication the “hot” drug related functions of the ventral PFC act to suppress the “cold” non-drug related activity of the dorsal PFC and cause the addict to engage overwhelmingly in attending to, seeking out and taking drugs without restraint
reward syste
mediates the acute rewarding and reinforcing effects of abused drugs–> important for initial stages of drug use and abuse
addiction and guilt
most individuals will likely have one or more lapses–danger is that guilt and diminished self-worth will engender hopelessness and lead to loss of control and a full blown relapse back to compulsive use.
disease
a pathological condition of the body that presents a group of clinical signs and symptoms and laboratory findings peculiar to it and that sets the condition apart as an abnormal entity differing from other normal or pathological body states
criticisms of disease model
- don’t know if same neuronal changes underly all drug addiction
- others view it as a behavior pattern that comes about as the result of interaction between many factors (environment, behavioral modeling, positive reinforcing effects of abuse drugs, the reinforcing consequences of avoiding or eliminating drug withdrawal and conditioning to drug related stimuli)
