Addiction

Question 1

Give examples of addictive drugs in clinical use (3)

Answer 1

e.g., opiates for pain relief,

Ritalin® to calm behaviour in children with ADHD,

cannabis oils to treat rare forms of epilepsy in children or muscle spasms caused by multiple sclerosis

Question 2

Give examples of addictive substances being present in over the counter products in the last century (4)

Answer 2

cocaine for toothache,

heroin products for coughs and colds,

Mrs Winslow’s morphine-based soothing syrup for teething in babies,

the alcohol-laced ‘Malt Nutrine’ to aid digestion in toddlers

Question 3

How is addiction diagnosed

Answer 3

11 point scale given in the DSM-V

mild: 2-3 symptoms; moderate: 4-6; severe: 7-11

Question 4

How does the criteria to diagnose addiction differ in the newer DSM from earlier versions

Answer 4

In the earliest versions of DSM, the symptoms of tolerance and withdrawal were emphasised

more recent iterations of DSM stress the pre-occupation of individuals to acquire drugs, maladaptive decisional processes, and continued use despite increasingly adverse consequences of out-of-control drug use

Question 5

Why were tolerance and withdrawal emphasised in the earliest DSM

Answer 5

defined by increasing levels of drug intake to maintain the same subjective experience, and which often co-occurs with a defined withdrawal syndrome – a set of symptoms triggered by the abrupt discontinuation of the drug (e.g., nausea, diarrhoea, seizures, irritability)

Question 6

Give the NHS and WHO definitions for addiction

Answer 6

NHS: “as not having control over using a drug to the point where it could be harmful to you”

WHO: “as a syndrome in which the use of a drug is given a much higher priority than other behaviours that once had a greater
value”.

Question 7

What proportion of the population does addiction affect

Answer 7

15-20%

Question 8

Give some risk factors of addiction (7)

Answer 8

age of first use (early onset carrying greater risk),

gateway drugs (e.g., nicotine, cannabis –though controversial),

gender (females > males),

socioeconomic circumstances (including poverty),

aberrant stress coping mechanisms,

pre-morbid traits
(anxiety, impulsivity, thrill seeking),

various co-morbid disorders such as conduct disorder, personality disorder, and ADHD

individual propensity for addiction is likely determined by a balance between risk and protective markers, which may be inherited or shaped by the environment

Question 9

What is interesting about ADHD being a risk factor for addiction

Answer 9

ADHD is often treated with drugs that have a high abuse liability such as amphetamine

may be self medicating underlying deficits in temperament, perhaps aspects of arousal and attention.
eg stimulants may be taken to improve attentional focus by reducing distractibility

Question 10

Is addiction based off nature or nuture?

Answer 10

shaped by both biological (genes) and environmental variables (in a roughly 50/50 manner)

Question 11

How was dopamine discovered to be a dominant neurochemical of the reward pathways

Answer 11

intra-cranial self-stimulation (ICSS)

Question 12

Which part of the brain has addiction research been focussed on

Answer 12

dopamine system

nucleus accumbens (NAc), a key forebrain region of the reward system, together with dopamine inputs to this region,as the primary substrates underlying the addictive properties of drug

Question 13

Why was the idea that NAc and its dopamine inputs involvement in addiction given added momentum?

Answer 13

all drugs of abuse, following an acute injection, increase dopamine release in the NAc

Question 14

What is the role of dopamine in reward pathways?

Answer 14

dopamine does NOT signal reward per se (or more precisely pleasure) but it does play a role in reinforcement learning – in other words in learning the predictive relations of reinforcers in the environment

Question 15

What did Schultz discover about dopamine

Answer 15

dopamine neurons encode reward prediction errors that enable learning to reward-related cues

Question 16

Describe dopaminergic neuron activity during reward presentation

Answer 16

dopamine neurons are active during the initial presentation of a reward, but habituate when the reward is fully predicted.

Activity then shifts to stimuli that predict the onset of a reward but decreases when expected reward are not delivered.

By increasing dopamine release, drug rewards are always better than expected

Question 17

What is the incentive salience sensitization theory

Answer 17

repeated exposure to drugs ‘sensitizes’ the mesolimbic dopamine system (ventral tegmental area → NAc) and in turn a motivation system that attaches valence to stimuli associated with drugs.

Question 18

What was Jane Stewart’s variation of the incentive salience sensitization theory (3)

Answer 18

discrete and contextual stimuli in the environment gain motivational significance through conditioning (i.e., they become incentives in their own right), and trigger feelings of craving and internal ruminations about the next drug binge

repeated drug
exposure progressively elevates dopamine release in the mesolimbic system, thereby
contributing to subjective feelings of ‘wanting’

indicated a clear separation between the motivation to seek drugs and the accompanying hedonic state

Question 19

Jane Stewart suggested, in dopamine, there is a clear separation between motivation to seek drugs and the hedonic state. Is there any evidence to support this

Answer 19

orally elicited ‘liking’ and ‘disgust’ responses were unaffected by the almost complete removal of dopamine from the striatum, and in fact were even slighted elevated!

this rules out an involvement of dopamine in hedonic reactions that instead implicate the endogenous opioid systems

Question 20

What are some problems with the incentive salience sensitization theory (3)

Answer 20

based on the behavioural response of rodents to repeated injections of drugs (↑ locomotor activity) that were given by the experimenter (not subject)

little evidence in humans that the mesolimbic dopamine system sensitizes with drug exposure

theory predicts that all individuals exposed to drugs would be become addicted

Question 21

What is the evidence in humans that the mesolimbic dopamine system sensitizes with drug exposure?

Answer 21

V little evidence for this
In fact, the opposite appears more likely with dopamine neurons becoming ‘exhausted’ with repeated cycles of bingeing and withdrawal

Question 22

Give 3 major theories of addiction

Answer 22

Incentive salience sensitization theory

Opponent process theory

Maladaptive conditioning theory

Question 23

What does the opponent process theory of addiction postulate

Answer 23

drugs engage two motivational systems, the first mediating positive reinforcement (people seek drugs as rewards to achieve a positive affective state), the second mediating negative reinforcement (people seek drugs to escape from the unpleasant symptoms of withdrawal). With continued drug use, tolerance develops to the positive effects, which encourages drug binges, while in the background, a deepening negative affective state develops. Eventually, negative reinforcement mechanisms come to dominate behaviour

Question 24

Describe the roles of different molecules in the opponent process theory

Answer 24

in anti-reward state: CRF, NA, and dynorphin upregulated

there is also a theorised reduction in dopamine and opioids that underlie reward state

Question 25

What is the idea of allostasis in the opponent process theory

Answer 25

reflects the dynamic change in mood set point caused by continued drug exposure (the so-called ‘wear and tear’ of drugs on the body).

Question 26

Addiction do which drugs fits the opponent process theory best?

which does it not work for

why

Answer 26

alcohol and opiates such as heroin and morphine, which produce obvious withdrawal signs,

works less well for cocaine and other stimulant drugs where less well-defined symptoms of dysphoria and irritability arise.

Question 27

What question does the opponent process theory pose?

Give a possible answer

Answer 27

r people take drugs to deliberatively lessen the intensity of withdrawal?

This may of course be a consequence of relapse, but re-initiation may well be driven by other factors, which compel people to use drugs

Question 28

What is the maladaptive conditioning theory of addiction

Answer 28

views addiction as a series of transitions involving specific learning processes

considers initial drug intake as a goal-directed experience, where behaviour is controlled by
the value of the outcome (an action-outcome or A-O association)

With increasing drug exposure, cues in the environment gain motivational significance, probably mediated in part by dopamine-dependent mechanisms, and progressively come to control behaviour. Thus, one can think of addiction as a shift from internal or volitional control to control mediated by external stimuli

Question 29

In the maladaptive conditioning theory, initial drug use is controlled by an action-outcome association. What does this mean?

Answer 29

This association
represents the likelihood that a specific response will deliver a specified outcome

eg taking drugs will make you feel good

Question 30

In the maladaptive conditioning theory, addiction is presented as a shift from internal or volitional control to control mediated by external stimuli. What is this psychological transition accompanied by?

Answer 30

shifts in behavioural control begin to emerge in different brain circuits:

drugs of abuse
progressively engage more dorsal areas of the striatum, in addition to initial effects within the ventral striatum (or nucleus accumbens)

Question 31

How did Porrino demonstrate the shift to progressively engage more dorsal areas of the striatum and NAc in addiction when there is a shift to externally mediated control?

Answer 31

in non-human primates trained to self-administer cocaine.

Question 32

The neural transition to involve the dorsal striatum and NAc, as postulated by the maladaptive conditioning theory, involves which regions specifically and what does this allow?

Answer 32

n encompasses sensorimotor regions of the dorsal striatum, especially dorsolateral
regions, and allows stimulus-response (or S-R) habits to dominate drug-seeking
behaviour

Question 33

What does the neural and psychological shift suggested in the maladaptive conditioning theory explain about addiction

Answer 33

how external stimuli through conditioning can trigger drug-seeking habits automatically (even if the drug is no longer sensed as pleasurable!).

Question 34

What questions arise from the maladaptive conditioning theory of addiction

Answer 34

the nature of
compulsion and whether a loss of flexibility over habits (a defining aspect of compulsion) depends serially on the development of habits in the first place or whether this develops within a parallel set of brain structures and circuits.

Question 35

Name a prime brain region implicated in the loss of control over habits

Answer 35

prefrontal cortex (PFC)

Question 36

What did PET scans of the PFC reveal about addiction

Answer 36

local metabolism in PFC (including the orbitofrontal cortex and cingulate cortex) was significantly reduced in abstinent cocaine users compared with age-matched healthy controls

Question 37

What does the reduction of local metabolism in the PFC in addicts suggest

Answer 37

suggests that in addition to affecting different areas of the striatum (aka. caudate putamen) drugs of abuse compromise those areas of the brain responsible for mediating behavioural self-control and inhibition

loss of top-down control from the PFC would allow the habit-based systems to dominate

Question 38

What happens to the connection between the PFC and the motor system in addiction

Answer 38

‘hypofrontality’ linked to reduced expression of dopamine D2 receptors in the caudate putamen (gate to indirect pathway)

Question 39

What did Volkow suggest about D2 receptors and hypofrontality in addiction?

How could this be remedied?

Answer 39

reduced D2 receptor expression would produce hypofrontality by decreasing excitatory input to the PFC from the thalamus

use of TMS (Trans-magnetic stimulation) to strengthen PFC networks.

Question 40

How did Ersche disentangle familial risk from addiction to study risk factors

what did she find?

Answer 40

study in sibling pairs, one addicted to stimulant drugs, the other not.

familial risk was predicted by the reduced connection strength of a circuit from the PFC to the caudate nucleus

Question 41

Ersche found that familial risk of addiction was predicted by the reduced connection strength of a circuit from the PFC to the caudate nucleus. What other studies support this?

Answer 41

naturally impulsive rats also had reduced connection between PFC and caudate

hyper-impulsive rats show reduced expression of D2 receptors in the NAc even prior to drug exposure

Question 42

hyper-impulsive rats show reduced expression of D2 receptors in the NAc even prior to drug exposure. what does this suggest about risk of addiction?

Answer 42

reduced D2 receptor expression in humans addicted to drugs may in part be a pre-existing risk marker for addiction