W10 - Substance Abuse ✅

Question 1

What is meant by Substance Abuse Disorder?

Answer 1

• A pattern of drug use in which people rely on a drug chronically and excessively and not for therapeutic reasons
• Addiction or dependence refers to being physically dependent on a drug in addition to abusing it
• Can pose a serious threat physically, psychologically, and even leads to death.

Question 2

Motivation for taking drugs?

Answer 2

Addictive substances promote:

1. Positive reinforcement - reinforcing stimulus immediately following a behaviour promote repeats of behaviour.
2. Negative reinforcement - removal of something unpleasant
   - increase tolerance after repeated used => taking drugs deal with withdrawal symptoms
   - explanation for start of addiction (coping mechanism)
3. Craving & relapse - elicit classical conditioned responses (increase in dopamine in response to drug stimuli)
   -> due to long-lasting brain changes

Question 3

Examples of health risks of substance abuse disorder?

Answer 3

• Cocaine – psychotic behaviour, brain damage, death
• Designer drugs – Untested, potentially contaminated
• Intravenous drugs – risk contracting infectious diseases, overdose and death
• Alcohol – cirrhosis of liver, increased risk of heart disease and stroke, Korakoff’s syndrome
• Smoking – increased risk of cancers, heart disease, stroke etc

Question 4

What is the dopamine pathway of positive reinforcement?

Answer 4

• Mesolimbic dopaminergic system (addiction starts)
• Release of dopamine in the nucleus accumbens (NAC)
• Produce long term changes in other brain regions – starting with VTA
• Changes in the VTA -> increased activation in regions receiving dopaminergic input from VTA.
• Important changes occur in the dorsal striatum (basal ganglia) -> movement control

=> changes only happen after continuous uses

Question 5

What are opiates and the neural mechanism?

Answer 5

• Heroin is the most commonly abused opiate.
• Tolerance -> gradual increase in dosage
• Needle use
• Transmission to unborn child
• Uncertainty of strength and what it can be mixed with

Mechanism: stimulates opiate receptors causing:

• Analgesia (inability to feel pain)
• Hypothermia
• Sedation (Tegmentum)
• Reinforcement (VTA & NAC)

Question 6

What are stimulant drugs? (e.g. cocaine, amphetamine)

Answer 6

1. Cocaine: deactivates dopamine transporter proteins -> blocking dopamine reuptake
2. Amphetamine: inhibits dopamine reuptake & stimulates the release of dopamine from terminal buttons

=> Highly addictive, but destroying the dopamine site in NAC causes significant loss of reinforcing effect

Question 7

What is nicotine neural pathway?

Answer 7

• Smoking stimulates nicotinic acetylcholine receptors
• Nicotine is associated with the release of dopamine in the NAC -> reinforcing
• Damage to the insula disrupts smoking addiction

Question 8

What is alcohol neural pathway?

Answer 8

• Increases activity in mesolimbic pathway dopamine
• Anxiolytic and Sedative effects
• Two major sites of action:
  1. Indirect antagonist at NMDA receptors (glutamate)
  2. Indirect agonist at GABA receptors
• Increase sensitivity of receptor after alcohol effect can trigger seizure
• Trigger the release of endogenous opioids => increase in opioid receptors with abstinence is associated to alcohol cravings

Question 9

Case study for alcohol adverse effect? (Korsakoff syndrome)

Answer 9

Case study: Jimmie G, talk about his past memories in present tense, can’t form present memories

• Usually in alcoholics who are malnourished
• Lack of vitamin B1 in the brain and worsen by the toxic effects of alcohol
• Damage to thalamus and mammillary bodies -> important for encoding new memories

Question 10

What is cannabis neural pathway?

Answer 10

• Tetrahydrocannabinol (THC) -> principal psychoactive component of cannabis
• THC also has stimulating effect on dopaminergic neurons
• Cannabinoid Type 1 (CB1) receptors mediate most of the psychotropic effects of THC
• Blocking CB1 receptors abolishes the high produced by smoking cannabis & influence effect of other drugs (e.g. heroin, alcohol, nicotine)

Question 11

The link between heredity & drug abuse?

Answer 11

• Study by Kendler et al. (twin studies on different substance abuses)
• Environment = drug use & influence
• Genetics = determining whether the person becomes addicted
• ~40-60% of the vulnerability to addiction can be attributed to genetic factors

Question 12

What are the methods of therapy available for drug abuse?

Answer 12

1. Prescription drugs: e.g. opiate addiction is treated with methadone/buprenorphine to block the effect of opiate & produce weaker effect -> weaken cravings & reinforcing
2. Immunotherapy: vaccines specific to substance abused
3. Deep brain stimulation (DBS): implanting electrodes within specific areas -> produce electrical impulses that regulate abnormal impulses (high risk)
4. Transcranial magnetic stimulation (TMS): less invasive than DBS
   - efficacy in reducing tobacco
   - diminishing effect over time on nicotine cravings.