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Flashcards in Last Class Drugs Deck (28)
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Addiction: What is it?

Drug addiction involves:
- repeated consumption of drug (natural or synthetic)
- an overpowering desire or need (compulsion) to
continue taking the drug and obtain it by any means
- a tendency to increase the dose
- detrimental effects on the individual and society
Drug addicts are habitual drug users who continue to take a drug despite its adverse effects on their health and social life.


Drug addiction poses serious problems

▪ Alcohol
- car accidents, fetal alcohol syndrome, Korsakoff’s syndrome, heart disease, intracerebral hemorrhage

▪ Smoking
- Lung cancer, heart attack, stroke, less healthy babies, babies with smaller brains.

▪ Cocaine
- psychotic behaviour, brain damage, death by overdose, competition for lucrative and illegal markets, causes violent deaths.

➔ Addictive drugs stimulate brain mechanisms of reinforcement responsible for positive reinforcement. We do it cuz drugs are like chocolate.


Positive Reinforcement

▪ Positive reinforcement increases the frequency of behaviour because it is regularly followed by an appetitive stimulus.
- e.g. a food (the appetitive stimulus) will positively reinforce a lever press (the behaviour)

▪ Addictive drugs have positively reinforcing effects.
If the drug is inhaled or taken i.v., the response or act of taking the drug will be positively reinforced.

▪ Positive reinforcement is immediate and powerful


Positive Reinforcement and Drug Abuse

▪ Drug effectiveness is greatest when the reinforcing stimulus occurs immediately after the response.

▪ Rats will enter a maze arm where the small amount of food is delivered straight away rather than enter an arm where he has to wait to get a large food reward ➔ small immediate rewards are preferred over large delayed rewards (Logan, 1965)

▪ Most addictive drugs have immediate effects.
Heroine, faster than morphine

▪ A drug addict seeks a sudden “rush” produced by the fast
acting drug.

▪ The immediate, reinforcing effects of an addictive drug can for some individuals overpower the recognition of the long-term aversive effects.


Negative Reinforcement

▪ Negative reinforcement increases the frequency of behaviour because of the removal of an aversive stimulus.
- e.g. a rat will press a lever (the behaviour) to prevent the occurrence of a foot shock (the aversive stimulus).
▪ Negative reinforcement is NOT the same as punishment.
- negative reinforcement increases frequency of behaviour e.g. “if I take another shot, my withdrawal symptoms will disappear.”
- punishment makes the behaviour less likely to occur. e.g. “Everytime I smoke cannabis, I vomit.”


Temporal discounting

Longer delay, higher chance change preference.
Seen in variety of behaviours , like gambling or procrastination


Effects of Physical Dependence

People who are physically dependent on drugs show:
- tolerance: a decreased sensitivity to the drug due to continued use.
- withdrawal symptoms: opposite effects of the drug itself when the person stops taking the drug. Kicking the habit in rehab, show restless kicking behaviour, literally. Cold turkey, cold sweats!

Positive reinforcement provokes drug taking in the first place but negative reinforcement ensures that withdrawal effects go away.


Dependent vs addiction

Depednatcny is like insulin shots! Medical.
Not addicted.

But the addicts to drugs, cannot survive without it,
Psych issue.
Show tolerance and withdrawal.

Fine line I think.


Craving and Relapse
▪ Why do addicts crave drugs and why does the craving occur after long periods of abstinence?

- When an addictive drug activates the mesolimbic dopaminergic system, it gives incentive salience to the stimuli that are present at the time of drug taking.
- e.g. drug paraphernalia (bong, pipe, syringe, spoon, mirror, razor blade).

- Stimuli with incentive salience elicit craving or “wanting” (Robinson and Berridge, 2003).

Shift from action, (as becomes automatic) to visual cues/stimuli. Cog to I guess


incentive salience

When an addictive drug activates the mesolimbic dopaminergic system, it gives incentive salience to the stimuli that are present at the time of drug taking.



Animals quickly learn to press a lever to get an injection of drug (self-administration), and develop a physical dependence to it.

▪ They will show withdrawal symptoms when the drug is removed


Hedonic value is not associatied with

Likeing, it causes acquisition of drug addiction

incentive salience is important to liking! After.


Reinstatement Model of Drug Seeking

▪ Animals first trained to self-administer a drug in the presence of a light.
▪ The lever press response is extinguished by replacing the drug with saline.
▪ The animal eventually stops making lever responses.
▪ A “free” injection of drug is administered OR a stimulus with
incentive salience is presented (e.g. a light).
▪ The rat starts to lever press again.
▪ The reinstatement (relapse) of a previously extinguished response provides a model for the craving that motivates drug-seeking behaviour in former addicts.


Mesolimbic System
If dopamine transmission is blocked in the nucleus accumbens, a “free” shot of drug will

▪ NOT reinstate lever press responses (Grimm and See, 2000).

Addictive drugs (e.g. PCP, cannabis, amphetamine, cocaine, etc) trigger the release of dopamine in the nucleus accumbens (White, 1996).
The sight of smoking related images produces greater activation in the nucleus accumbens in smokers (David et al., 2005).


Prefrontal Cortex role in drug abuse,
Note card gambling study Iowa gambling task.

• Cocaine reinstates cocaine-seeking behaviour in rats by stimulating neurons in the prefrontal cortex that activate neurons in the nucleus accumbens via a glutamatergic pathway.

• Activation of the prefrontal cortex is directly related to craving.

• People with ventral and medial prefrontal lesions perform poorly on gambling tasks because they are attracted by the large payoffs. This is dominated by the immediate gratifcation of the large win (or the “high” produced by the drug).

• Prefrontal cortex of cocaine abusers is less active than that of subjects during abstinence (Volkov et al., 1992).


Prefrontal cortex activation is inversely related
to the amount of cocaine consumed each
week (Bolla et al., 2004)

Prefrontal cortex is less activated when addicts are performing tests of frontal function, and they perform poorly brain is damaged!


Reduced Prefrontal Gray Matter in Schizophrenics and Alcoholics

Abnormalities in prefrontal cortex may be a common factor in schizophrenia and substance abuse.

We do not know if preexisting abnormalities increase the risk of these disorders, or whether the disorders cause the abnormalities.

Less gray matter and esp pfc lower activation.


Commonly Abused Drugs: Opiates, characteristics

• Heroin is the most commonly abused opiate drug. Semi synthetic of mr phone from opium poppy

• Tolerance develops quickly and increasing amounts of drug must be consumed to achieve the “high.” ➔ crime provides money to support habit.

• Unsanitary needles increase exposure to AIDS or hepatitis.

• The user might receive an unusually large dose because of the uncertainty about the strength of any given batch. Note designer drugs. Parkinson's due to this.

• Opiates (including morphine and codeine) are addictive analgesics.


Lack of Responses to Morphine in Rats with Targeted Mutation of μ Opiate Receptor
3 receptors?

• The μ (mu) and δ (delta) receptors are responsible for reinforcement and analgesia. Stimulation of κ (kappa) receptors produce aversive effects.

• Mice with mutation targeted against μ receptors are insensitive to the reinforcing
and analgesic effects of morphine (Matthes et al., 1996).


Activation of Receptors in the Nucleus Accumbens is Sufficient but not Necessary to
Reinforce Behaviour

• The reinforcing effects of opiates are produced by activation of neurons in the mesolimbic dopaminergic system and release of dopamine in the nucleus accumbens.

• BUT, 6-OHDA (6-hydroxydopamine) lesions of the nucleus accumbens disrupts lever pressing of rats for injections of cocaine but has NO effect for injections of heroin.!

➔ Unlike other addictive drugs, opiates do not need to trigger dopamine release by neurons in the mesolimbic system to reinforce behaviour
Hijack brain!


Stimulant Drugs: Cocaine and Amphetamine

• Stimulants such as cocaine and amphetamine’s primary effect is to increase neural and behavioural activity.

• Cocaine and amphetamine act as potent dopamine agonists but they act in different ways
- cocaine binds (dopamine reuptake inhibitor) with and deactivates dopamine transporter proteins thereby blocking reuptake of dopamine.

- amphetamine stimulates the release of dopamine

So work in different ways

• Methamphetamine is similar to amphetamine but considerably more potent

• Freebase cocaine (“crack”) is smoked and enters the blood supply of lungs and reaches brain very quickly.


Stimulant Abuse Produces Adverse Long-Term Effects on the Brain

• Prior methamphetamine abusers show a decrease in the number of dopamine transporters in the striatum despite having abstained from the drug for 3 years


Nicotine characteristics (first 6)

Nicotine (I)
• Nicotine accounts for more deaths than the so called “hard”drugs. Despite seemingly less bad than others.

• Nicotine is carcinogenic

• 50% of people who start smoking at adolescence and continue to smoke into adulthood will die from a smoke- related disease.

• By 2020, it is estimated that tobacco will be the largest single health problem worldwide accounting for 8.4 millions deaths a year.

• Is smoking a “habit” rather than an “addiction.”
Tobacco is legalized, cultural norm...
• People who regularly take tobacco are compulsive drug users though


4 other things to know about nicotine

Nicotine stimulates nicotinic acetylcholine receptors.

• It also stimulates the mesolimbic pathway and causes dopamine release in the nucleus accumbens, has reinforcing properties.

Injections of nicotine increase dopamine concentration in nucleus accumbens.

Nicotine receptors are found in both the VTA and nucleus accumbens. Where dopamine receptors lie.


Alcohol has two primary sites of action:

an indirect agonist at the GABAA receptor and
an indirect antagonist at the NMDA

Both actions trigger apoptosis (cell death).

Highest dug leading to car accidents.


Alcohol Removes Inhibitory Effect on Social Control
• At low doses, alcohol is
At high doses,


• it causes poor coordination and sedation.

• Alcohol releases the punishing effects of aversive stimuli.
(i.e. it increases punished responding).

➔ That’s why we lose our inhibitions when we drink, tolerate some pain.


punished responding

if a lever press leads to an electric shock, the rat will stop lever pressing.
- If rat is given alcohol, it will start lever pressing again


Cannabis characteristics

• The active ingredient in cannabis (marijuana) is THC (delta-9-tetrahydrocannabinol).

• Usual mode of consumption is to smoke it but it can also be ingested orally.

• Cannabis works on endogenous cannabinoid receptors.

• High doses of cannabis impair psychological functioning, especially memory.
- the hippocampus releases endogenous cannabinoids.

• Like other drugs, cannabis stimulates release of dopamine in the nucleus accumbens.