Substance Abuse Addiction and reward mechanisms

substance abuse models. dopamine pathways. addiction preqs

what separates drug use from drug addiction

drug use becomes drug addiction when you continue using despite the harm it causes, and when you cannot control your usage

Substance use Disorder criteria

interferes with life, distress,

their problems and symptoms need to be persistent
mild 2-3

moderate 4-5

severe 6+

Categories of SUD symptoms (ISRP)

Impaired control

social problems

Risky use

Physical dependence

impaired control (SUD)

loss or control or use/consumption

(ex. ends up drinking more than intended)

social problems (SUD)

affects their relationships, school, work
(attendance, responsibilities, mistreatment/neglecting)

risky use (SUD)

using the substance in situations that would be risky

(while driving, using unclean needles, and is aware despite knowing risks)

physical dependence (SUD)

becomes tolerant to the substance and need more to illicit same effect and goes through withdrawal when stoping drug

Moral Model (models of Drug Abuse)

aims to blame the person for their addiction, claims they are immoral, lack self discipline, tied to religion sometimes (not religious enough and thus ended up druggy)

Disease model (models of drug abuse)

treats person as sick, addiction is a medical condition tried to
medically treats substance abuse

helps research addiction

doesn’t completely explain how addiction happens

Physical Dependence Model

aka withdrawal avoidance model
says people need to continue drugs to avoid neg withdrawal symptoms
doesn’t explain addiction

why people start taking drug before the body us dependent, no symptoms

doesn’t completely eliminate withdrawal (ex. nicotine patch in theory should work) there must be smth else too

Model of Positive Reward (what is it, how is mesolimbocortical pathway, VTA, nucleus accumbens, and endocanabinoid sugnalijg invovled) how tested

proposes addiction is propelled by reinforcement
(rewarding feelings of drugs cause addiction)

stimulates the mesolimbocaortical pathway (a dopamine pathway for reward and reinforcement(

increases dopamine of neurons in the VTA (ventrateg) causing more dopamine release in nucleus accumbens

also endocanabinoids or opiods can increase rewarding effects by signaling in this reward circuit

tested via self stimulation

describe the first intracranial self stimulation experiment

provides electricity in certain area in brain (placed in wrong areas by mistake ) and discovered that the rodents liked getting stimulation in mistake area, and would continue presses lever for electrical stimulation there

Self Administration studies (animal: what is it, connection to natural rewards)

after reward stimulation areas were discovered there were studies where they had animals press the lever to get small amt of drugs

these regions are the same as the ones our brain uses for natural rewards like food and water

why do animals self administer drugs before they become dependent on it?

they do so because of the rewarding effects, because at that point they aren’t dependent, they are not trying to avoid withdrawal symptoms

What is the Mesolimbocortical pathway and its structure (brain regions)?

one of two dopamine pathways that goes from the VTA (ventral tegmental area) of the midbrain to the

nucleus accumbens (primary reward region)

links or projections to limbic system (amgdayla, hippocampus), and the cortex (PFC, insula)

what proof is there that the mesolimocortical pathway facilitates reward

brain self stimulation studies have shown that

1. the VTA is activated during any rewarding experience as shown by Mapping of self stimulation sites

2. During self stimulation dopamine release increases

3. dopamine agonists increase self stim, dopamine antagonists reduce it

4. lesions in MLC pathway interrupt self stimu

how does Cocaine act in mesolimbic dopamine pathway?

will act in the nucleus accumebsn dopamine terminals: blocks reputake of dopamine so it stays for longer increasing dopamine binding

how does nicotine act in the mesolinbic dopamine pathway

nicotinic receptors found all over but it will activate nicotinic receptors on the VTA’s dopamine neurons, causing them to fire more

how do opiods acts in mesolimbic dopamine pathway

it inhibits inhibitory neurons in the VTA, allowing dopamine neurons to fire more

how do psychodelics aft in mesolimbic dopamine pathway

they don’t really activate this pathway

What dopamine really does within the brain

what are the two aspects of REWARDS

Liking and wanting

Liking

the pleasure of an experience from a reinforcer (smth that makes a behaviour more likely to happen again)
(ex. animal presses lever to get food)

wanting

the need to get the reinforcer (craving, motivated)

what is the difference between wanting and liking

does dopamine cause wanting or liking

wanting or motivation to get the reinforcer is reduced if the dopamine system is leisoned. still get pleasure from eating , or dugs but no motivation to obtain

this is because dopamine creates wanting (crave drugs, drug cues, cues can trigger craving) not a pleasurable experience

what does dopamine really do?

it makes you motivated to obtain rewards

people can still continue doing something even if the liking pleasure is gone, they will still feel the wanting to get the reinforcer

Sensitization

the opposite of tolerance, repeated exposure makes you more sensitive/responsive to the drug, and sometimes the wanting/ need to obtain trhe drug

Hyperactive Dopamine Signaling

due to repeated drug use there is repeated activation of the mesolimbocortical system

leading neurons to better communication with eachother

their system becomes better at getting dopamine and makes them want it even more, while liking (pleasure) does not increase. so addicts can still feel the want without even enjoying the substance anymore

what are factors for Vulnerability to Drug use (BFPS)

Biological

Family environment

Personal characteristics

Social and environmental factors

Biological factors (vulnerability)

genetic predisposistion, sex differences

Family environment (vulnerability)

having family conflict

Personal (characteristics (vulnerability)

impulsive, aggressive, bad emotional regulation

personality traits

Social and Environmental factors (vulnerability)

grew up in a community with drug use, peer group does drugs

Treatment options or medical application of what we’ve learned

treat or manage discomfort of drug cravings : nicotine patches, treat withdrawal symptoms

find alternatives to the drug

block action of addictive drug

Change Metabolization of Drug

Reduce the brain’s reward system

Vaccines

less relevant

what is naxolone?

a competitive antagonist for opioid receptors binding there instead of opiates, and blocking preventing activity, and displacing the binded opiates

it reverses opioid overdoses

does not treat addiction