Neurobiology of Addiction and Opiates

Question 1

outline the dopaminergic reward pathway

Answer 1

Question 2

which 2 drugs cause the most significant increase in dopamine release

Answer 2

ampethamines and cocaine

Question 3

what is the reward pathway involved in

Answer 3

it acts as a motivating signal, incentivises behaviour

it is involved in normal pleasurable experiences

Question 4

what happens when you over stimulate the reward pathway, eg take too many drugs

Answer 4

the dopamine receptors downregulate, so a tolerance to reward is developed

this means the theshold for all rewards is increased - normal experiences arent pleasurable and more drug is reuqired for same effect

Question 5

is downregulation of the dopamine receptors in reward pathway reversible?

Answer 5

yes?? over time, but the changes persist despite prolonged abstinence - this is a trigger for relapse

Question 6

what is positive reinforcement

Answer 6

reinforcing stimulus, eg money for doing homework

Question 7

what is negative reinforcement

Answer 7

an annoying stimulus is removed after a particular behavour, eg nagging stopped after dishes done

Question 8

is drug addiction drive by positive or negative reinforcement

Answer 8

positive in the initial stages

negative in the later (eg to get rid of withdrawals, life seems dull)

Question 9

what is the role of the prefrontal cortex

Answer 9

planning complex cognitive behaviour, personality expression, decision making and social behaviour

keeps emotions and impulses under control to achieve long term goals –> puts the breaks on the reward pathway

Question 10

where does cortical maturation begin and end

Answer 10

back to front, from Mi to frontal gyri, prefontal cortex develops last

Question 11

what is the significance of the late development of the pre frontal cortex

Answer 11

it is not fully developed till 20s (marshmallow test)

this means that the parts of the brain that control exectuive functioning mature later than limbic (emotional) systems –> teens show strong stimuls reward, minimal judgement and impulse control

Question 12

what is the significance of starting addictions early

Answer 12

the PFC is vulnerable during development

synpatic plasticity - the earlier drugs start the longer the relatonship is

Question 13

what effect can learned drug associations have

Answer 13

can cue internal states of craving eg opening a fag packet

Question 14

what is the role of the orbito frontal cortex in addiction

Answer 14

provides an internal representation of the saliency of events and assigns a value to them –> creates a motivation to act

in addicts, this area is activated a lot when they are presented with a drug cue –> craving

Question 15

how is the PFC affected by addiction

Answer 15

PFC is dysfunctional - no longer putting breaks on reward pathway or OFC

too much dopamine going around

Question 16

do genetics have an influence on addiction?

Answer 16

Yes! large

They may affect: the way we respond to drugs metabolically; behavioural traits that predispose us to take drugs; how rewarding we find drug taking. Influence receptor levels, e.g. if there are low dopamine receptors there is a higher risk.

Question 17

what does acute and chronic stress do in the reward pathway

Answer 17

acute triggers the release of dopamine in the reward pathway –> motivate dependent to take drugs

chronic causes downregulation of dopamine receptors - reduces sensitivity to normal rewards and encourages exposure to highly rewarding behaviours.

Question 18

what pharmacodynamic features make heroin so addictive

Answer 18

it reaches peak plasma levels very quickly in blood stream - euphoria

short half life so plasma levels drop quickly - physiological withdrawal

Question 19

what is another name for heroin

Answer 19

diamorphine

Question 20

how is diamorphine made from morphine

Answer 20

add 2 acetyl rings

Question 21

metabolism of heroin

Answer 21

diacetylmorphine (heroin) - 6 mono acetyl morphine - morphine

Question 22

detection of which substance is indicative of heroin use

Answer 22

6MAM

Question 23

where would you detect 6MAM

Answer 23

in urine, present for 6 hours after use

Question 24

what does detection of morphine in urine indicate

Answer 24

could be heroine or codeine (the active metabolite of codeine is morphine)

Question 25

what do opiate users teeth look like

Answer 25

bad - may be due to analgesia stopping them feeling dental pain also, suppression of salivary production causes stomach acid to rot teet

Question 26

when do withdrawal symptoms tend to occur

Answer 26

6-8 hours after

Question 27

symptoms of opioid withdrawal

Answer 27

* Dysphoria and cravings * Agitation * Tachycardia and hypertension * Piloerection – hairs on arms stand on end * Diarrhoea, nausea and vomiting * Joint pains * Yawning * Rhinorrhea and lacrimation ## Footnote *​sympathetic overactivity*

Question 28

what drug can be used for withdrawal symptoms

Answer 28

Lofexidine - inhibits the release of norepinephrine in the CNS and PNS has no effect on opioid cravings

Question 29

local complications of IV use

Answer 29

cellulitis, abscess, thrombophelbitis, necrotizing fasciitis

Question 30

endocarditis in IV drug users - which valve and bacteria

Answer 30

tricuspid valve - right sided S Aureus (flucloxacillin)

Question 31

systemic complications of IV use

Answer 31

Hep B, Hep C, HIV

Question 32

which other drugs are implicated in opioid related death

Answer 32

gabapentin and pregabalin are used to enhance the effects of opioids (anticonvulsants) diazepam and etilzopam are implicated too

Question 33

which drug is used in an opioid overdose

Answer 33

Naloxone - opioid antagonist

Question 34

does heroin cause psychosis or delirium

Answer 34

no

Question 35

what is the basic principle in opiate substitution therapy

Answer 35

replace a short acting opioid with a long acting one - buprenorphine or methadone

Question 36

dosing of Buprenorphine/Methadone

Answer 36

once daily under supervision

Question 37

is Buprenorphine or Methadone usually used

Answer 37

Methadone can be given in liquid form which is preferable - harder to divert. is a full agonist Buprenorphine is a partial agonist and is only available as a tablet

Question 38

what is opidate detoxification

Answer 38

achieving complete abstinence from all opiates

Question 39

what is the main risk of opioid detoxification

Answer 39

death with relapse - physical tolerance levels lower but psycholoigcally the patient is still dependent and will often relapse and take the same high dose they did when they had a tolerance

Question 40

rate of relapse within 1 year

Answer 40

70-80%

Question 41

what is contingency management

Answer 41

Rewarding positive behaviours to reduce illicit drug use and/or promote engagement with services receiving methadone maintenance treatment, and to improve physical health care.