Lecture 19-22

Question 1

Desomorphine (3)

synthesized from + morphine + high

Answer 1

• synthesized from codeine
• Analog of morphine but more potent and addictive
• Shorter high than heroin (1.5h vs 4-8h)

Question 2

Streetuse of desomorphine (3)

synthesize + dangerous bc + streetname

Answer 2

• Easy to synthesize (cheap/fast)
• dangerous as it is not purified (contains codeine, gasoline, iodine, red phosphorous, HCl, paint thinner)
• Streetname is Krokodil

Question 3

The effects of Krokodil:

+ chronic users

Answer 3

• blood vessel degradation
• Blood vessel rupture
• Gangrene (blood flow to an area of tissue is cut off)
• Amputation
• Scaly appearance
• Chronic users dont survice for 2-3 years

Question 4

History of drugs: Willow Bark (2)

contains + relieves

Answer 4

• Contains salicin, transformed into salicyclic acid (the precursor to aspirin)
• Relive pain and fever

Question 5

History of drugs: Shamanism (2)

What + example

Answer 5

• healer through trance (“First she goes/falls into a deep trance, and then the spirit voices start to speak through her”), plant-based medicines, in the context of a local religion
• Entheogen: Psychoactive substance used in a religious, shamanic or spiritual context

Question 6

A shift to more centralized religions resulted in a preiesthood in control of healing, for example (3):

Ex + pages/prescriptions + treats….

Answer 6

• Elbers Papyrus: ancient Egyptian medical document
• 110 pages long containing more than 800 prescriptions
• Waspstrings, crocodile bites, baldness, constipation, headaches, sweaty feet, arthritis, inflammation, heart disease, cancer etc

Question 7

History of drugs: Middle ages

Answer 7

• Vikings warriors assumed to have ingested mushrooms (Amanita muscaria) which has psychoactive properties or henbane Hyoscyamus niger a atropine (acts as a competitive, reversible antagonist of muscarinic receptors: an anticholinergic drug) resulting in increased energy and wild behaviour in battle

Question 8

History of drugs: Drug use and witchcraft

Answer 8

• Induced hallucinations and sensation of flying by consuming brews made of mandrake, hebane, and belladonna

Question 9

History of drugs: Licking toads (2)

What contains + derivative

Answer 9

• Sweat glands contain a powerful hallucinogen (5-MeO-DMT) as well as bufotenine (raises blood pressure and heart rate)
• Both of which are tryptamine derivative

Question 10

History of drugs: 19th century (3)

2 invention/advances + there was no…..

Answer 10

• Advances in chemistry resulted in the identification and purification of morphine as the active ingredient in opium and cocaine in coca
• Invention of the hpodermic syringe Purified substance to be injected to BS to increase potency
• No drug control laws (Pain+cough syrups for kids have morphine and codeine)

Question 11

Drug addiction becomes medicalized (3):

3 timelines

Answer 11

• 1870: American Association for the Cure of inebriates
• 1935: Alcoholics Anonymous became popular
• 1950: World Health Organization declares alcoholism a disease

Question 12

Today we accept the —— model of addiction

Answer 12

disease

Question 13

What defines addiction (2)

what + the cycle

Answer 13

• A chronic relapsing behavioural disorder
• A compulsive drug seeking and drug use:
  1. Craving: Strong urger to take the drug (something in brain changed, neuroadaptivity)
  2. Remisssions: Drug-free periods
  3. Relapse: Drug use recurs, despite negative consequences

Question 14

DSM IV (2000) refers to substance-related disorders (2):

The 2 categories

Answer 14

1. Substance abuse: Less severe, may or may not lead to substance dependence (not yet there)
2. Substance dependence: More severe, akin to addiction

Question 15

Substance use disorder (2)

What + the scale of symptoms

Answer 15

• A pattern of maladaptive substance use over at least a 12-month period, that had led to significant impairment or distress.
• 2-3, 3-5, 6+ # of have the symptoms mild-moderate-severe

Question 16

Internet Gaming disorder (4)

described…but + classified in + what + criteria

Answer 16

• Described in the DSM, but not enough evidence to be a unique mental disorder
• Only behavioural addiction classified in DSM-5
• Repetitive use of internet-based games often with other players that leads to significant issues with functioning
• 5 of the following criteria must be met within one year

Question 17

Positive reinforcement model (2):

what + experiemnt

Answer 17

• Most drugs of abuse act as positive reinforcers: consuming the drug strengthens whatever preceding behaviours was performed
• IV catheter connected with mice is filled with drugs. The mice press on lever and drug is given.

Question 18

Positive reinforcement model

Self-adminstration studies: Fixed-ratio (FR) schedule (5)

What + curve + ascending + descending + high []

Answer 18

• Ratio schedules involve reinforcement after a certain number of responses have been emitted. The fixed ratio schedule involves using a constant number of responses. For example, if the rabbit is reinforced every time it pulls the lever exactly five times, it would be reinforced on an FR 5 schedule
• The typical dose-response functions is an inverted U-shaped curve
• Ascending curve = increased reinforcing effectiveness of drug (animal is working for it)
• Descending curve = satiation to drug, aversive reactions, side effects (hyperactivity, sedation)
• At high concentration, cocaine is more reinforcing than heroin.

Question 19

** EDIT/UPDATE SLIDE*

A progressive ratio (PR) schedule of reinforcement (4)

what + example + increased until + BP?

Answer 19

• an increasing response requirement for reinforcer delivery over successive sessions
• Lever press on a continous reinforcement schedule (1 to 1) to a low fixed ratio scheduled (ex: FR-5)
• FR schedule is increased progressively until the animal stops responding
• Higher breaking point for higher morphine dose

Question 20

Breaking point

Answer 20

The response ratio/dose that is not reinforcing anymore or at which responding ceases

Question 21

Positive reinforcement

How is relaspse in self-adminstration studies done (4)?

Answer 21

1. Induce forced abstinence (take the drug away but lever is still there)
2. Reinstatement of drug-seeking behaviour:
   - Delivering a small dose (drug priming) sip of alcohol
   - Subjecting animal to stress
   - Environmental cues previously paired with drug delivery (expose animal to tone, light, sound that was paired to drug delivery but you dont give the drug)

Question 22

Explain the process of extinction and reinstatement in positive reinforcement FR studies (4):

Answer 22

1. Rats are hooked onto a machine, self-adminstration schedule FR of cocaine, they are initially trained.
2. 14 days to extinguish response. Press lever no drugs and response is distinguished
3. End of 2 week, rapid fall of responding. Then either exposed to stress, environmental cues or drug priming.
4. High rate of response (relapse)

The graph depicts typical data from rats that were first stabilized on IV drug (e.g., cocaine) self-administration using an FR schedule of reinforcement. The red data points show the number of responses per session on a lever that is linked to drug delivery. Each drug infusion is accompanied by presentation of a cue, which is typically a light or a tone. The purple data points show the number of responses per session on a control lever that has no consequences when pressed. After 12 days of self-administration in this particular paradigm, the animals are switched to a 14-day extinction (E) phase in which pressing the drug lever no longer elicits either drug delivery or cue presentation. Note the rapid falloff of responding during this phase. However, if the drug-paired cue is presented, if the animals are subjected to stress (e.g., foot shock), or if a priming dose of the drug is administered by the experimenter, the animals resume a high rate of responding on the drug lever despite the fact that the drug is still withheld (E14). This phenomenon, which is termed reinstatement, is considered to be an animal model of relapse to drug use after abstinence in drug addicts.

Question 23

What issues/concerns might you have with self-adminstration studies (2)?

Answer 23

• additional stress (catheter/isolation)
• we dont know why addiction is starting in first place

Question 24

The rat park experiment (3)

what + results

Answer 24

• Rats given a choice between standard drinking water or morphine solution
• 2 Groups, isolation and enriched housing
• Results showed that isolated rats consumed significantly more morphine than those that were socially housed. Perhaps consumption of drugs are from environmental factors like discomfort.

Question 25

Gateway Theory (2) | What + pathway

Answer 25

- Use of a drug at one stage in the sequence serves as a risk factor that predicts an increased likelihood of using drug at the next stage. - Someone starts legal drugs (alcohol, nicotine) -> progress to marijuana -> heroine/cocaine

Question 26

# Gateway Theory The use of marijuana is associated with increased probability of ------

Answer 26

further drug use

Question 27

Gateway theory/hypothesis supports (3):

Answer 27

1. People who use marijuana are more likely to develop an alcohol use disorder 2. Early exposure to marijuana decreases activity of dopamine reward centers in the brain in adulthood. 3. Heightened behavioural response to further THC or other drugs (cross-sensitization) with prior THC exposure.

Question 28

Gateway theory/hypothesis arguments (2):

Answer 28

- Most people that use marijuana dont go on to use other "hard drugs" - Alcohol and nicotine usage increase the likelihood that someone will go on to use other drugs

Question 29

Progression wheel towards addiction: (3)

Answer 29

1. Periods of preoccupation with drugs and anticipation of upcoming use 2. Periods of drug intoxication, in some cases associated with bingeing 3. Periods following drug use characterized by withdrawal symptoms and negative effects

Question 30

Physical dependence model (4) | what + reinforcement + may be bc of

Answer 30

- Attempts at abstinence following chronic drug use results in withdrawal symptoms/ abstinence syndrome - Relief of withdrawal symptoms promotes drug-taking behaviour (relapse) - Negative reinforcement - May be because of changes in the brain

Question 31

Biopsychosocial model

Answer 31

- A balance between factors that promote drug addiction and those that are protective - A consideration of multiple factors is necessary to understand addiction: behaviour, pharmacology, biology, psychology

Question 32

Disease/medical model

Answer 32

- Addiction is tied to changes in brain structure and functions and fundamentally it is a brain disease - "sinners" - Disease concept of alcoholism

Question 33

Criticisms of Disease/medical model (4)

Answer 33

- all experiences we encounter affect the structures and functioning of our brain, often permanently. - There are no laboratory tests that can identify the cause as with other types of disease - Some people recover from addiction without treatment. - Those who question the disease model argue that a brain-centric view pays too little attention to the whole person, attend to mroe psyosocial aspect not just brain.

Question 34

Reward circuit

Answer 34

- Neurons originate in the ventral tegmental area (VTA) of the midbrain and terminate in the nucleus accumbens (NAcc), amygdala (AMG), Hippcampus, and prefrontal cortex (PFC).

Question 35

Drugs of abuse increases the activity of the:

Answer 35

mesolimbic dopamine pathway

Question 36

Psychostimulants such as cocaine and amphetamine exert their rewarding effects by the reward circuit. Dopamine activity is mediated by: (3)

Answer 36

- Nicotine: directly releasing DA from dopaminergic terminals in the NAcc (stimulating nicotinic cholinergic receptors in the VTA) - Cocaine/amphetamine: by blocking DA reuptake after its release (increase dopamine) - Heroin: Inhibition of GABA release so they cannot inhibit DA neurons anymore leading to more DA release

Question 37

How do we know DA is important experiment?

Answer 37

1. Teach aminal to cell administrate (bar press for cocaine/heroin) 2. Lesion dopamine neuron (Kainic acid lesion of nucleus accumbens, distript DA release) 3. See what happens to self-adminstration Results: Damages to the nucleus accumbens is negatively correlated with cocaine intake. Intake is less if they is more damage. Animal is not getting as much rewarding effect and this not self-adminstrating.

Question 38

How do we know DA is important? Monkey expirement

Answer 38

1. Place electrodes in VTA to record activity of DA neurons while monkey perform task 2. Present monkey with rewarding stimulu like fruit juice. DA neuron fired phasically. Not trained so no prediction 3. When monkey's are trained with light. Association forms. Learned that light perdicts future reward. Becaus they know, they will receive juice when light is on. Now DA neuron fire when light goes on. 4. When monkey's are presented with light, DA neurons are activated. After receive reward (juice) we dont see any DA neuron activated. 5. Monkey now react to conditioned stimulus, cells dont respond to reward. It is the prediction of reard that they care about instead of the reward. 6. Found that if reward is not delievered after light, then DA activity is depressed significantly. Monkey knew when reward is expected and if received. (more unhappy abt expectation not getting then just not getting in the first place with no expectation) 7. DA neurons are encoding expectation of reward and the response to it (if its there). 8. Shows that DA neuron change time of fire/activation, before association they respond to reward, after association they respond to cue. ## Footnote Neurons always fire to proximal cue, principle of addiction, get out of the enironment!

Question 39

Pigeon reward circuit

Answer 39

- 2 groups: train to peck for food reward and train to peck for H2O rewarded. - They changed behaviour with light. Lick in drinking group for light and bite light for food group - They are reacting to conditioned stimulus as a reward. Not the actual light.