Addiction

Question 1

substance use disorder

Answer 1

chronic relapsing disorder
1. compulsion to seek + take drug
2. loss of control in limiting intake
3. emergence of negative emotional state without drug

11 diagnostic criteria
severity of disorder = number of criteria

DSM-5 → emphasis towards behaviours; psychosocial impacts

Question 2

biopsychosocial disease

Answer 2

biological factors increase risk but other factors contribute to development and relapse

SES, homelessness, social isolation, trauma

Question 3

cycle of addiction

Answer 3

initial drug use
continued drug use
drug withdrawal
compulsive drug use

Question 4

initial drug use

Answer 4

determined by - genetics, mood
genetics: impulsivity = predisposition to rapid reactions; differences in monoamine metabolism = different drug effects

Question 5

continued drug use

Answer 5

driven by positive reinforcement: pleasant stimulus = higher likelihood of response
positive effects of drug
incentive salience → overtime becomes incentive sensitization

Question 6

incentive salience

Answer 6

motivation for rewards learned by previous associations

Question 7

incentive sensitization

Answer 7

amplification of drug ‘wanting’ triggered by drug cues
physiological response to expectation even before actual consumption

Question 8

drug withdrawal

Answer 8

unpleasant symptoms can drive craving and relapse
brain develops mechanisms to fight shifts against homeostasis → revealed in the absence of drug
negative reinforcement: desire to avoid symptoms drives continued use

Question 9

compulsive drug use

Answer 9

shift from impulsive to compulsive use
compulsivity: behaviour perseveres in face of adverse consequences
shift from positive reinforcement → negative reinforcement

Question 10

neural circuits involved in drug use

Answer 10

mesolimbic dopamine system
prefrontal cortex
central amygdala

Question 11

mesolimbic dopamine system

Answer 11

dopamine neurons in VTA project to ventral striatum and prefrontal cortex

salient stimuli triggers dopamine release = motivated behaviour

Question 12

dopamine neurons in substantia nigra

Answer 12

project to dorsal striatum
movement initiation

proximity to motivation = movement response to reward

Question 13

rate of dopamine increase

Answer 13

phasic burst = rapid spike: salience and reward
tonic response = slower release: anticipation

deficits in dopamine signalling are associated with depression and anhedonia

Question 14

phasic dopamine

Answer 14

signals salience of rewarding cues; not necessarily reward

VTA dopamine activity in monkeys → without a reward, an associated stimulus leads to inhibition of dopamine firing

Question 15

drugs of abuse

Answer 15

all evoke dopamine release but different mechanisms
1. opioids - bind to mu receptors (inhibitory GPCRs) on GABA interneurons in VTA = disinhibition
2. psychostimulants - block dopamine transporter → inhibit dopamine reuptake = increased levels of dopamine in synapse
- psychostimulant reward requires midbrain dopamine

Question 16

neurocircuitry adaptation

Answer 16

sensitization of mesolimbic dopamine system = same amount of drug evokes larger dopamine response → drug craving
incentive sensitization through compulsive use
recalibrates dopamine thresholds for natural rewards

lower tonic dopamine levels = depression

Question 17

prefrontal cortex

Answer 17

glutamate afferents in cortex project to striatum = increase dopamine release
drug cues activate orbital frontal cortex in addiction

glutamate release increases AMPA receptor expression and long-term potentiation at dopamine synapses → increased dopamine signalling

Question 18

central amygdala

Answer 18

nucleus in limbic brain associated with fear + anxiety
release of CRF causes anxiety

higher CRF levels associated with drug withdrawal

Question 19

treatment

Answer 19

combine pharmacological and behavioural interventions

Question 20

pharmacological interventions

Answer 20

1. block positive effects of drug
2. make withdrawal easier

Question 21

chronic drug use - impact on dopamine signalling

Answer 21

1. sensitized drug-evoked phasic release
2. decreased tonic levels during withdrawal

Question 22

partial dopamine agonists

Answer 22

normalize adaptations of chronic drug use to return dopamine levels to a homeostatic level
1. blunts drug-evoked dopamine effect = antagonist
2. restores dopamine deficit during withdrawal → only partially activates receptor - alleviates symptoms

Question 23

treatment of drug withdrawal

Answer 23

maintain abstinence
drug that targets the same receptor as drug of abuse but has safer therapeutic profile

Question 24

agonist replacement therapy

Answer 24

maintenance on opioid agonist + CBT
blunts symptoms of withdrawal
longer half-life → avoid high/crash cycle
ex. buprenorphine - partial mu agonist