Chapter 9: Drug Abuse And Addiction Flashcards
What is addiction?
Addiction is a collection of behaviors
- compulsive drug seeking and drug using behaviors
Characterized by a chronic tendency to relapse
- periods of abstinence interrupted by drug use
- Chronic, relapsing behaviored disorder
Drug Abuse
Problematic drug use that might meet DSM-5 criteria for mild/ moderate substance use disorder
Addiction
Problematic drug use that might meet DSM-5 criteria for severe substance use disorder
Addiction is characterized by a […] tendency to […]
Addiction is characterized by a chronic tendency to relapse
Behavioral aspects of addiction
- compulsive drug-seeking and drug-using behavior
- Cravings- strong urges to take the drug
Chronic, relapsing aspect of addiction
- long-lasting
- drug-free periods followed by relapse to drug use
Impulsive Stage of Addiction
- Binge intoxication
- Pleasurable effects
- Abstinence; Neural affect
- Reward craving
Compulsive Stage of Addiction
- Prolonged intoxication
- Relief
- Prolonged abstinence/ Negative affect
- Relief craving
DSM-5 drug classes
- Alcohol
- Caffeine
- Cannabis
- Hallucinogens
- Inhalants
- Opioids
- Sedative-hypnotic and anxiolytics drugs
- Stimulants
- Tobacco
- Others
Substance Use Disorders
A pattern of use that is “problematic,” leading to “significant impairment and distress”
*continues using substance despite significant substance-related problem
Substance-induced disorders
Substance-specific syndromes due to recent substance use
Addiction potential of a substance is influenced by route of administration
IV and inhalation (greatest abuse potential)
- Rapid absorption, fast onset, short duration
Drugs of abuse share 2 important properties
Positively reinforcing
Rewarding
Positive reinforcing
- consuming the drug strengthens whatever preceding behavior was performed
- how hard an animal will work for a drug
Rewarding
- the positive experience associated with the drug
- the “high” and feeling of relaxation
Tool for studying positive reinforcement
Drug self-administration
How hard will an animal work for drugs?
- drug response (continuous reinforcement (fixed ratio))
- after certain point, drug starts to interrupt behavior
- drug satiation, aversive reactions, behavioral disruptive side effects - Discriminative stimulus also contribute to drug-seeking behavior
Breaking point- response ratio at which responding ceases
Rewarding properties if drugs are commonly evaluated using
Place conditioning
- animals conditioned to associate a particular chamber with morphine show preference for that chamber
Electrical self-stimulation
- drugs of abuse sometimes have aversive effects - drugs of abuse decrease electrical self-stimulation
Withdrawal from ethanol […] threshold for electrical self-stimulation of reward pathway
Withdrawal from ethanol increase threshold for electrical self-stimulation of reward pathway
- reinforcement is less rewarding that it was during initial ethanol use
Natural recovery
Abstinence with little to no treatment
Relapse to drug use is modeled by […]
Relapse to drug use is modeled by reinstatement
- Forced abstinence
- Renewed responding
- 3 stimuli
Forced abstinence
Extinguishes drug seeking behavior (CR)
Renewed responding
Some stimuli are effective in reinstating drug-seeking= reinstatement
Stimuli
- Drug priming (US)- delivering small dose of drug to animal
- Stress
- CS’s- anything paired with drug uses (environmental cues)
Biopsychosocial Model
Includes pharmacological, biological, and psychological/ sociocultural factors that influence addiction risk
CS’s, stress, or drug exposure […] drug-seeking
CS’s, stress, or drug exposure reinstate drug-seeking
- reinstatement is an animal model of relapse to drug use after abstinence
Drug detoxification
Elimination of drug form one’s system and passage through the abstinence syndrome
Impulsive Stage
- driven by positive reinforcement, drug reward properties
- reward circuitry- activated
- generally occurs early in drug using behavior
Compulsive Stage
- driven by negative reinforcement; removal of negative stimuli (withdrawal/ abstinence)
- recruitment of anti-reward circuitry
- generally occurs later in drug using behavior
Stages of substance use
- Preoccupation with anticipation of obtaining and using substance
- Binge use and intoxication from substance
- Withdrawal and associated negative effect
The […] posited that strong affective responses are followed by their opposite
The opponent process model posited that strong affective responses are followed by their opposite
Opponent process model
Neural mechanisms responsible for affect were organized such that any stimulus that provides initial strong affective reaction automatically sets in motion on opposing affective response that is experienced after initial stimulus ends
Opponent process model: nondependent
A process: reward
B process: withdrawal
Opponent process model: dependent
A process: tolerance
B process: anti-reward
Reward pathway
VTA—> Nuc Acc (VS)—> ventral pallidum
*also medial frontal cortex, amygdala, septal area, and olfactory tubercles
Antireward
Central nucleus of amygdala—> BNST
Increased NE, increased cotropin- releasing factor, increases dynorphin
*after reaching addiction
DA is critical in reward
- Mesolimbic and mesocortical pathways
- incentive sensitization theory
- Opioid, GABA, nACh receptors are also important
- D2 affinity»_space; D1 affinity; D1 receptors are more important for drug reward
Mesolimbic and mesocortical pathways
- DA transmission from VTA to N accumbens and PFC
- Essentially all drugs of abuse increase DA signaling in the reward pathway
Incentive sensitization theory
Drug liking vs wanting
- certain stimuli become extremely salient and acquire incentive properties
Liking: euphoria, “high”
Wanting: craving
- the incentive salience
- stimuli associated with drug use become attention-getting, desirable
Alcohol
Increases GABAa and DA in NAcc
[…] underlie the transition to addiction
Neuroadaptations underlie the transition to addiction
- Tolerance
- Recruitment of the antireward system
- Allostasis of hedonic state
Neuroadaptation
Pertains to persistent neurobiological changes that can encompass NT activity, gene expression, cellular structure, and neural circuitry
Allostasis
Physiological, behavioral, or psychological variable that is repeatedly challenged maintained stability by changing its set point
Tolerance
Decreased activity in the reward circuitry
Recruitment of the antireward system
Increased release of NE, CRF, and dynorphin
Allostasis of hedonic state
Change in set points addict uses to feel “normal”
Dysfunction in the PFC contributes to the […] phase
Dysfunction in the PFC contributes to the preoccupation/ anticipation phase
- PFC is essential for behavioral control
- PFC exerts “top-down” control over striatal systems
3 main pathways for PFC dysfunction
- Dorsolateral circuit that projects from dorsolateral PFC (DLPFC) —> dorsolateral caudate nucleus
- Ventromedial circuit that connects anterior cingulate cortex with NAcc
- Orbitofrontal circuit that projects from orbitofrontal cortex
PFC dysfunction in addiction is characterized by
Intrusive thoughts; craving (motivation); poor impulse control
The transcription factor […] is important in driving molecular changes underlying addiction
The transcription factor FosB is important in driving molecular changes underlying addiction
- Drug administration rapidly induces FosB
- FosB-induced changes in gene expression
- epigenetic mechanisms (changes in gene expression increase risk)
Drug administration rapidly induces FosB
N Acc and dorsal striatum
FosB-induced changes in gene expression
- DNA methylation represses transcription (chromatin compaction)
- Histone acetylation promotes transcription (opens chromatin)
Genetic Factors of Addiction
- 0.3-0.8 for heritability of substance use disorders seen in adoption and twin studies
- Common disease-common variant hypothesis
- Common disease-rare variant hypothesis
Common disease-common variant hypothesis
Genetically based susceptibility to neuropsychiatric disorders stems from pool of risk-conferring gene alleles are possessed in common throughout population
Common disease-rare variant hypothesis
Neuropsychiatric disorders are extremely heterogenous in genetic risk alleles
