Week Four - Addiction Neuroscience

Question 1

What is the definition of addiction?

Answer 1

There is no single, universally accepted definition of addiction.

Question 2

Why are there criticisms of addiction being a ‘brain disorder’?

Answer 2

Because it disregards human decision making and choice

Question 3

What does the DSM-5 regard addiction as?

Answer 3

substance-related and addictive disorder

Question 4

Substance-related disorders are classified into what 2 groups?

Answer 4

Substance use disorders

Substance-induced disorders

Question 5

What do Substance use disorders involve?

Answer 5

Involve a cluster of cognitive, behavioural, and physiological symptoms as well as continued use of the substance despite significant substance-related problems.

Question 6

Substance abuse disorder disorder contains what 9 classes of drugs?

Answer 6

alcohol, cannabis, hallucinogens, PCP, opioids, inhalants, sedatives, stimulants, or tobacco.

Question 7

What do Substance-induced disorders include?

Answer 7

substance intoxication, substance withdrawal, and other substance/medication-induced mental disorders.

Question 8

severity of substance-induced disorder depends on what?

Answer 8

How many criteria are met
2-3: mild
4-5: mod
6+: severe

Question 9

What is the cause of of substance use disorders and addictive behaviour?

Answer 9

No single cause, but a product of enviro and physiological factors

Question 10

Why are animal models ‘limited’ or criticised?

Answer 10

Because humans manipulate the addiction environments

Question 11

How does the drug cycle begin?

Answer 11

Positive reinforcement: pleasurable effects reinforce drug use

Negative reinforcement may also however explain initial drug use in those who use drugs to escape distress/stress

Question 12

Why does compulsive drug-taking occur?

Answer 12

Because the rewarding effects of drug use are reduced and there is a need to achieve a state of homeostasis (neg reinforcement)

Question 13

Addiction shares features of what 2 disorders?

Answer 13

Impulsive and compulsive

Question 14

When does negative reinforcement occur during drug taking?

Answer 14

When drug taking is driven by the need to reduce anxiety/stress

Question 15

A shift from pos to neg reinforcement is evident when?

Answer 15

An individual transits from an impulsive disorder to compulsive disorder

Question 16

What is a common feature of all addictive drugs?

Answer 16

They activate reward pathways in the brain by triggering the release of dopamine

Question 17

What do reward pathways refer to?

Answer 17

The connections between striatal, midbrain, limbic and prefrontal regions of the brain known as the mesocorticolimbic pathways

Question 18

Where do drugs such as amphetamine, cocaine, nicotine and morphine as well as food and sex elevate dopamine transmission?

Answer 18

in the nucleus accumbens (heavily innervated by dopamine fibres)

Question 19

How do drugs create an illusion in the nucleus accumbens?

Answer 19

By creating an illusion and tricking the brain by imitating the release of chemicals associated with motivation

Question 20

Lesioning the dopamine system at the level of the nucleus accumbus does what?

Answer 20

prevents the acquisition of cocaine and nicotine self-administration in rodents suggesting that dopamine mediates the enforcing effects of each.

Question 21

What further substantiates dopamines involvement in addiction - parkinson’s?

Answer 21

D agonists often block the rewarding effects of drugs.

Humans with PD report having blunted effects of stimulants

Question 22

What is drug addiction often characterised by?

Answer 22

Anhedonia (failure to experience rewarding stimuli)

Question 23

In addition to the dopamine system, the serotonergic system plays a critical role in what?

Answer 23

Mediating the experience of pleasure as evidenced by depression research

Question 24

What other 2 NT also play a role in addiction?

Answer 24

GABA

• opiates increase dopamine in part by removing the inhibitory influence of GABA on dopamine releasing cells
• GABA agonists have been found to reduce drinking, decrease craving ad improve sleep in those with alc use disorder

GLUTAMATE
- low glutamate levels in peeps with alc use disorder

Question 25

Addiction leads to changes in (5)

Answer 25

synaptic plasticity dendritic size and spines white and gray matter up/down-regulation of receptors intracellular signalling pathways

Question 26

What is synaptic plasticity?

Answer 26

The ability of synaptic connections to strengthen or weaken as a result of increased or decreased activity

Question 27

What two receptions have received attention in SP?

Answer 27

NMDA and AMPA glutamate receptors

Question 28

NMDA and AMPA glutamate receptors are typically involed in what?

Answer 28

long-term potentiation

Question 29

What is LTP?

Answer 29

LTP refers to increased efficiency of neurotransmission and plays a critical role in learning and memory.

Question 30

Changes in SP are observed in what?

Answer 30

Drug sensitisation (an enhanced response to the drug that is observed following repeated exposure; also known as reversed tolerance)

Question 31

What did amphetamine treatment do to mices dendritic arbours/spines?

Answer 31

It increased the size of the in the nucleus accumbens and increased the number of spines these neurons had on their dendrites

Question 32

What was elevated in animals treated with amphetamine? | What did this demonstrate?

Answer 32

The number of glutamatergic synapses in the nucleus accumbens. This region of the brain becomes hyper-excitable following chronic amphetamine exposure

Question 33

Robinson et al. (2001) found structural changes in dendrites located in the prefrontal cortex of rats that self-administered cocaine. What were these changes?

Answer 33

The dendrites of cells of the rats that self-administered cocaine were misshapen, with large, bulbous structures at their tips. - linked to impaired decision making and judgement

Question 34

Current technology does not enable what?

Answer 34

Dendritic density and size measurements in humans

Question 35

Studies have consistently reported what in regard to grey matter and substance use disorders? (2)

Answer 35

Gray matter volume reductions in the prefrontal regions and additional mesocorticolimbic structures. Drug craving was negatively associated with gray-matter volume

Question 36

White matter and substance use disorder findings? (2)

Answer 36

Reduced white matter has been found in participants with substance use disorders. Significant loss of cerebral white matter found in postmortem and living individuals with alcohol use disorder

Question 37

Rivkin et al. (2008) reported that children exposed to cocaine, tobacco, marijuana, or alcohol in utero had what?

Answer 37

Smaller head circumference and white and gray matter

Question 38

Opioid use disorder is associated with changes to what?

Answer 38

White matter and gray matter changes in brain regions implicated in addiction including those involved in the regulation of impulse control, as well as in reward and motivational functions

Question 39

Several studies have found what in regard to receptor regulation? Volkow and colleagues (1996)

Answer 39

Decreased density of postsynaptic dopamine receptors (D2) in participants with substance use disorder

Question 40

Chang, Alicata, and Volkow (2007) found reduced dopamine transporter density and reduced dopamine D2 receptors in what area of the brain?

Answer 40

The striatum

Question 41

Continued use of substances is associated with what?

Answer 41

Continued use is associated with complex intracellular changes.

Question 42

Intracellular changes are believed to be responsible for?

Answer 42

Tolerance, addiction and withdrawal

Question 43

What is one important intracellular change associated with drug addiction?

Answer 43

up-regulation of the (cAMP) pathway.

Question 44

What is CREB?

Answer 44

A protein that plays a key role in learning and memory.

Question 45

When is CREB induced?

Answer 45

Following chronic exposure to drugs such as stimulants and opiates.

Question 46

An increase in phosphorylated CREB correlates with what?

Answer 46

Diminished sensitivity to drug-induced reward.

Question 47

How is CREB linked with tolerance/dysphoria/withdrawal?

Answer 47

CREB provides a compensatory mechanism that responds to drugs

Question 48

Over-expression of ΔFosB does what?

Answer 48

increases sensitivity to the rewarding and reinforcing effects of stimulants

Question 49

What does the raclopride method allow?

Answer 49

Estimation of dopamine levels through competitive binding to D2 receptors

Question 50

After Methylphenidate-induced increases in the striatal dopamine in controls and in detoxified cocaine abusers what happens?

Answer 50

Cocaine abusers and alcoholics show decreased dopamine increases and report reduced reward effects of MP

Question 51

What can drugs cause?

Answer 51

Hypodopaminergia

Question 52

What is Hypodopaminergia

Answer 52

depletion of monoamine stores in the brain, inducing depressive-like symptoms

Question 53

What is Hypodopaminergia linked to? (2)

Answer 53

Anhedonia: inability or difficulty to experience pleasure Hypofrontality: decrease activation of PFC - compromising planning/decision making

Question 54

What is a challenge for neurobiology?

Answer 54

To understand why some individuals become addicted while others do not

Question 55

What is a key to the current challenge for neurobiology? How?

Answer 55

Differences in reward circuits Subjects with high d2 receptors = effects of MP not pleasant Subjects with low d2 receptors = MP effects are pleasant

Question 56

Overexpression of D2 receptors in the NAcb in rats did what?

Answer 56

Reduces alcohol preference and self-administration

Question 57

Impulsive rats were found to have what?

Answer 57

Lower D2 receptors

Question 58

In humans, low densities of D2 receptors were associated with?

Answer 58

Decreased metabolism in the orbitofrontal cortex - associated with OCD and impulsivity