BS42017 L3.1,2,3

Question 1

give examples of opiates (4)

Answer 1

morphine, codeine, thebaine, oripavaine

Question 2

give examples of endogenous opioids (4)

Answer 2

B-endorphin, met-enkephalin, dynorphin, endomorphins

Question 3

what exact substance is heroin and how does it differ to morphine?

Answer 3

diamorphine- it passes through the BBB more rapidly than morphine and then gets broken down

Question 4

name an agonist to each of the three types of opioid receptors

Answer 4

mu- DAMGO
delta- DPDPE
kappa- U50/ 488-H

Question 5

what does the mu-opioid receptor do? (3)

Answer 5

is responsible for reward feelings, recruits B-arrestin2, activates cell response pathways.

Question 6

what is the mechanism of opioid receptor tolerance relating to B-arrestin2?

Answer 6

• mu receptor gets sequestered into the membrane by B-arrestin2.
• The membrane endocytoses the receptor.
• This process is thought to be important in tolerance.
• When b-arrestin is recruited to the receptor it brings with it associated kinases that can signal other cellular effects, different to the g-protein ones.

Question 7

what are the 4 mechanisms of morphine tolerance?

Answer 7

1. receptor tolerance
2. cell tolerance and withdrawal
3. system tolerance and withdrawal
4. synaptic plasticity in tolerance and withdrawal

Question 8

what therapies are there for opioid use disorder? (5)

Answer 8

1. psychosocial therapies (CBT)
2. methadone (mu receptor agonist)
3. Buprenorphine (mu-receptor partial agonist and K-receptor antagonist). Combined with naloxone in suboxone with reduce potential for diversion.
4. naltrexone (opioid antagonist)
5. Detoxification- symptomatic relief- anti-inflammatory drugs; antiemetics; anti-diarrhoeal medications. Lofexidine (a2 adrenergic receptor agonist) or other opioids

Question 9

how does morphine act on the central dopaminergic pathway?

Answer 9

• when morphine is applied the GABA-ergic action potentials essentially stop
• baseline lowers slightly
• decrease in GABA inhibition results in increase dopamine release from the dopaminergic neurons

Question 10

what type of opioid receptors are required for morphine reinforcement?

Answer 10

mu receptors (MOP-/- mouse model experiment)

Question 11

which side effects of opioids is B-arrestin2 potentially involved in?

Answer 11

respiratory depression and constipation

Question 12

what does an absence of B-arrestin2 result in? (mouse model)

Answer 12

reduced morphine tolerance (tail withdrawal test)

Question 13

what is the influence of B-arrestin2 on morphine actions?

Answer 13

• increased basal analgesia mediated by MOPrs
• decreased morphine tolerance/dependence
• decreased respiratory depression
• decreased constipation
• decreased locomotion
• increased reward

Question 14

psychomotor effects (only in rodents not in humans) require which receptors?

Answer 14

mu-opioid receptors

Question 15

what is required for full locomotion associated with MOPrs?

Answer 15

B-arrestin2

Question 16

what functions does dopamine regulate? (5)

Answer 16

• locomotion
• cognition
• reward
• emotions
• endocrine function

Question 17

dopamine dependent disorders includes; (5)

Answer 17

• schizophrenia
• bipolar disorder
• depression
• Parkinson’s disease
• drug abuse/dependence

Question 18

what synthesises dopamine?

Answer 18

tyrosine hydroxylase (TH)

Question 19

what are the five main dopamine signalling pathways?

Answer 19

nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular and tuberhypophysial

Question 20

where do the nigrostriatal neurons originate from?

Answer 20

substantia nigra and VTA, projecting to the caudate putamen and NA respectively

Question 21

what are the types of dopamine receptors?

Answer 21

D1-5

D1-like are D1 and D5, D2-like are D2, D3 and D4

Question 22

what do the two kinds of dopamine receptors do to adenylyl cyclase?

Answer 22

D1 activates it, D2 inhibits it

Question 23

which kind of dopamine receptors are required for morphine CPP?

Answer 23

D2

Question 24

what do TH-/- mice show?

Answer 24

no morphine locomotion (restored by L-dopa injection)

still exhibit morphine reward

Question 25

stimulation of mouse locomotion is dependent on what?

Answer 25

D1 and B-arrestin2

Question 26

what makes D1 receptors associated with stimulation of mouse locomotion to morphine?

Answer 26

activation of ERK

Question 27

what does early life adversity do to opioid relapse behaviour?

Answer 27

increases it (ELA paradigm study)

Question 28

what is the theory of allostasis?

Answer 28

This model is proposed for brain changes that occur in the development of addiction that explains the persistent vulnerability to relapse long after drug-taking has ceased

Question 29

what is allostatic state?

Answer 29

When there’s not enough time inbetween an individual episode of drug/alcohol taking for the mood to return to normal then a drift occurs

Question 30

Why is methadone used to treat heroin addiction?

Answer 30

it has a more stable pharmacokinetic profile so the patient wont feel withdrawal symptoms or high sensation

Question 31

Is dopamine and/or dopamine receptors required for opioid reinforcement?

Answer 31

D2 receptors when knocked out reduce CPP to morphine- so are required for reinforcement. D1 receptors have no such effect on CPP.