2. Ch 9 Addiction Flashcards
McDowell county WVA
intense poverty
harm reduction programs - gives out clean needles
treat addiction as disease
Methadone and Subaxone
Methadone - inhibits pain but no effect on reward system
Subaxone - partial agonist of opioid receptors, reduces reward
Drug use effects
Reduces grey matter in PFC (less control)
Heroin turns on/off genes for glutamate
opioid use reduces DA synthesis and reduces DA receptors, less motivation
Opioid withdrawal symptoms
withdrawal pain
“opioid refugee” can’t get more drugs, still pain
releases stress, shaking/pain
babies with withdrawal
childhood trauma inc. risk of addiction
Vancouver and addiction
“in site” clinics, supervised opioid use
reduces ODs
test fentanyl/other drugs for toxins
Wolfgang Schultz Dopamine Monkeys
DA neurons fire to the signal that a reward is coming, not the reward itself
pattern recognition - seek to understand pattern and gamble more
Spike to surprising rewards (surprise of a stimulus)
ReQuip drug
to treat Parkinsons, mimics DA
caused gambling symptoms (stop = parkinsons returned)
War on Drugs
controlled substances act of 1970 made schedule of drugs (made DEA/ prison for drugs)
war on drugs failed
states try decriminializing drugs but no treatment options
DSM V and addiction
9 chemical addictions, and “non-substance related” disorder - gambling
substances activate the reward system, risk of misuse
Criteria for how harmful drug is
Lethality - margin of safety
Long-term health - cancer/infection
Impaired Brain Function - ability to do cog/motor
Dependence liability - capture ratio = likelihood to become addict
Harm to family/community - domestic violence/medical costs
Modern conceptions of drug addiction
compulsive nature
craving
addiction lasts long time, followed by remissions and relapse despite negative consequences
cycle of addiction
3 categories of harm
determining harm of a drug
- physical harm
- tendency to induce dependence
- effect on family/community
Paradox of addiction
how can someone maintain such a destructive pattern of addiction
Can’t model destructive effects in animals (negative aspects come much later after euphoria)
Addiction potential of a substance
influenced by route of administration
PO = slow absorption
IV/inhalation = fast and direct (hypodermic needle invention 1858, soldiers disease
Positive reinforcers, drug reward, and craving
Pos. Reinforcers = reinforce beh’r. strong reinforcers have strong abuse potential
Drug Reward = positive experience with drug, high/relax/alertness reinforce the drugt oo
Craving = urge to take drug
Physical Dependence of Drug
abstinence attempts lead to withdrawal
- motivates taking drug again, negative reinforcement to feel normal again, continuous loop
Harrison Act 1914 - forced absitence withdrawal
Transition from impulsive to compulsive
Impulsive stage - motivation is positive reinforcing, goal-oriented, reward system
Compulsive stage - motivation is negative reinforcement, relief from withdrawl, habit like, anti-reward system
Conditioned Withdrawal
classical conditioning of withdrawal if in same environment, can happen after being sober
Effects of meth stimuli on brain
Ventral Striatum and medial Frontal Cortex activated from meth stimuli in meth users, not control
Hard though because no within subjects, no pre-drug baseline
Addiction as a disease and medicalization of it
the changes to the brain are preventable/treatable/changes bio/can last lifetime
Addiction as a disease can be treated - shift away from moral weakness, reduces guilt, alcoholism declared disease by WHO
Disease Model and criticisms
arose from alcoholism
DSMV called it substance use disorder (impairment/severity/maladaptive life)
Criticisms acknolwedge brain changes but - can only identify by clinical signs no lab tests (like most psycho disorders), addiction can be stopped personally, shift addiction if have other positive reinforcers (rat park, social rats self-admin’d less than lonely rats)
matters bc guilt/relapse, insurance companies
Maladaptive allocation of behavior
people with substance use allocate beh’r towards drug, need to reallocate towards healthier reinforcers
2 methods of studying drug reward
Conditioned Place Preference
Intracranial Self-Stimulation - threshold is increased when in withdrawal from chronic abuse (need more drug to feel normal), threshold decreases in acute administration
Self-administration in durg use
Fixed Ratio dose-response curve is inverted U
at low doses, # reinforcers (bar presses) increases to get drug
at high doses, # reinforcers declines due to satiation/aversive reactions
Breaking Point
breaking point of when animal stops during increasing FR
increases with higher doses
Relapse studies
Force absitenence
reintroduce stimuli known to provoke responding
- priming (little bit drug)
- stress
- environmental paired cues
this causes mice to do drug be’hr again, press lever again
Reward Circuit
Mesolimbic DA pathway
VTA to NAcc
central role in acute rewarding/reinforcing effects
essential for some drugs (stimulants), but not all (alc/heroin)
Aspects of DA
DA involved in many aspects in reward circuit
Pleasure - emotional, pleasure of drug use
Incentive Salience - motivation, wanting vs liking
Reward prediction - cognitive, dopamine signals about predictions error
DA as Pleasure Transmitter
partial DA agonist Abilify caused sex/gambling
Release of DA in NAcc caused euphoria
BUT, tyrosine depleted diet (no DA) caused no decrease in euphoria w/ cocaine
DA as Motivation
DA important for incentive salience quality of drug
Incentive salience model - addiction shifts from liking (euphoria) to wanting (craving). No change in liking, wanting increases in addiction
tyrosine depletion diet decreased CRAVING, no reduction in euphoria/liking
Further, bee DA levels elevated in search of food (crave) not during eating (like)
DA as Reward Prediction
VTA DA firing in monkeys
fired when rewards were given at first, then associated with a stimulus
then fired to the conditioned stimulus, suppressed if juice didn’t come
DA neurons respond to predictive rewards if they have difference in expectance (fire when unexpected cond. stimulus and suppress if no expected juice)
Two types Neuroadaptations taking drugs
Within-System adaptations in reward circuit lead to down-regulation of activity
Between-System adaptations lead to recruitment of anti-reward system
Anti-Reward System
activated in withdrawal
shift from impulsive to compulsive
relevant for alc/opioids
Reward system uses VTA DA neurons on NAcc
Anti-Reward uses CRF neurons on NE neurons = stress and amygdala, take drug to neg. reinforce away the stress
Delta FosB gene
transcription factor
induced in NAcc
overexpression of it leads to enhanced sensitivity of drug
early life stress = epigenetic changes, more risk of substance use disorder
2 brain changes in drug addiction
Reduced Striatal D2 Receptors - lack of impulse control/planning, inc. drug salience
Structural/Functional abnormalities in PFC - poor executive function/valuation/incentives
Rehab and Treatment
abstinence doesn’t work, centers profit off people, aggressive sales tactics
Medication Assisted Treatment (MAT) - mu-opioid partial agonists to help reduce cravings
Stroke victims w/ damage to cingulate/prefrontal have less cravings - TMS mPFC treatment for addiction
