Lecture 24: Drug Abuse and Addiction

Question 1

When is use a disorder? DSM 5: Substance Use Disorder

Answer 1

• Combines former categories of abuse & dependence w/ continuum from mild to severe
• Each substance as a different use disorder
– alcohol use disorder, stimulant use disorder
• 2-3 symptoms from list of 11 symptoms

Question 2

DSM impaired control

Answer 2

(1) taking more or for longer than intended, (2) unsuccessful efforts to stop or cut down use, (3) spending a great deal of time obtaining, using, or recovering from use, (4) craving for substance.

Question 3

DSM social impairment

Answer 3

(5) failure to fulfill major obligations due to use, (6) continued use despite problems caused or exacerbated by use, (7) important activities given up or reduced because of substance use.

Question 4

DSM risky use

Answer 4

(8) recurrent use in hazardous situations, (9) continued use despite physical or psychological problems that are caused or exacerbated by substance use.

Question 5

DSM pharmacological dependence

Answer 5

(10) tolerance to effects of the substance, (11) withdrawal symptoms when not using or using less.*

Question 6

Models of substance use

Answer 6

• Initial use: positive reinforcement
– Use to get high …
• Chronic use: negative reinforcement
– Use to avoid how awful feel when not high … bring back to “normal”

Question 7

Cocaine action

Answer 7

• Re-uptake inhibitor for monoamines
• Inhibits DA, NE, and 5HT transporters
• Reward mediated via effects on DAT

Question 8

Amphetamines

Answer 8

• Including methamphetamine
• Used for weight loss, to stay awake
• Side effects: insomnia, anxiety
• Rapid addiction
• Reverses DAT
• Long-term use of meth
– Damage to frontal lobe
– Depletion of DA levels
– Damage to temporal lobe (memory) and limbic system (emotion)

Question 9

Opiates

Answer 9

• Heroin, morphine, codeine
• Depressant effect: relaxation, analgesia, euphoria
• Bind endogenous opioid receptors that bind endorphins
– Mainly μ (Mu R)
• Highly addictive
– Increases pleasure by binding μ
– Increases wanting by binding DA Rs
• Long-term use: addiction, attention and memory problems

Question 10

Marijuana

Answer 10

• Tetrahydrocannabinol (THC) = active ingredient
• Relaxation, content mood, perceptual & cognitive distortions; anti-nausea
• Endogenous cannabinoids (anandamide) [chocolate also has anandamide-like chemicals!]

Question 11

Marijuana action

Answer 11

• THC is partial agonist of cannabinoid Rs
• THC increases DA release in NAC
• Hippocampus has large number of THC receptors - THC impairs episodic memory, particularly spacial memory

Question 12

The reward system

Answer 12

Hedonic & motivational effects of natural rewards and drugs of abuse

Question 13

Dopamine

Answer 13

DAergic system starting in VTA in midbrain -> amygdala, hippocampus, and nucleus accumbens

Question 14

What can be rewarding?

Answer 14

• Effectiveness of reward greatest when closely temporally linked to reinforcing stimulus
– E.g. Heroin passes through BBB more quickly, is faster than morphine
• All natural reinforcers cause DA release from NAC
– Addictive drugs “hijack” this system

Question 15

Dopamine and reward

Answer 15

• More DA released under deprived conditions than under non-deprived conditions
• DA involved in facilitation of LTP in NAC, amygdala and PFC
• Operant conditioning: dopamine release sets value of a reinforcer, and blocking dopamine decreases reinforcement
• Robinson and Berridge introduced an important distinction between wanting and liking aspects of reward
– Dopamine appears to be especially important in wanting a reward … can want but not like

Question 16

Remember homeostasis? (what causes addiction)

Answer 16

• Maintain physiological levels within optimal bounds
• Alterations take place for this to be achieved
• E.g. flood brain with X neurotransmitter what might happen?
– To receptors? Numbers? Sensitivity?
• Allostasis

Question 17

Start of addiction

Answer 17

• Operant conditioning: behavior -> reward, so continue behaviors
– First changes seen in VTA – single dose of addictive drugs can cause enhanced strength in excitatory synapses in VTA on DA neurons
• Behaviors become habit
– Longer-term changes in the regions VTA projects to:
• Reward areas (NA)
• Areas involved in compulsive, habitual actions
(dorsal striatum)
• DA release in drug addicts by just viewing drug paraphernalia

Question 18

What discriminates those who become addicted?

Answer 18

• About 10-12% users become addicts
• Heredity (~40%-60% of vulnerability)
• Age
– Adolescents most vulnerable
– Delayed PFC development
– 50% of addiction cases begin ages 15-18; very few after age 20
• Sex differences
• Environment (access, stress)
• Low behavioral inhibition is a risk factor for substance abuse

Question 19

Stress as trigger: mechanism

Answer 19

• Stress is known trigger for drug use
• Stress -> release of stress hormones, including corticotropin releasing hormone (CRH)
• Administration of CRH –> reinstate drug-taking behavior
• Drug to block CRH Rs -> reduces likelihood of relapse
• The VTA in reward system has CRH Rs that mediate this effect

Question 20

Is recovery possible?

Answer 20

• Relapse rate 40-60%
• Behavioral therapy effective
• Treatment of withdrawal symptoms