Opioids

Question 1

What is opium?

Answer 1

The product of heroin metabolism

Diacetyl-morphine (diamorphine)

Question 2

What are the endogenous opioids?

Answer 2

Beta-endorphins

Enkephalins

Question 3

What is the function of the opioid system?

Answer 3

Provide reward for pro-survival activities

Provide defence against pain

Question 4

How do opioids produce a pleasure response?

Answer 4

Inhibits the GABA mediates IPSCs in the post-synaptic dopamine neuron

Inhibits APs in the presynaptic GABA neuron

Overall —> more DA

Question 5

Describe the structure of the opioid receptor

Answer 5

7 membrane spanning domains which interact with intracellular G proteins

Question 6

What are the types of opioid receptor?

Answer 6

Mu
Delta
Kappa

(NOP not a true receptor)

Question 7

Which gene codes for mu opioid receptors?

Answer 7

OPRM1

Question 8

Which gene codes for delta opioid receptors?

Answer 8

OPRD1

Question 9

Which gene codes for kappa opioid receptors?

Answer 9

OPRK1

Question 10

What is the main selective agonist of mu opioid receptors?

Answer 10

DAMGO

Question 11

What is a selective agonist of delta receptors?

Answer 11

DPDPE

Question 12

What is the selective agonist of kappa opioid receptors?

Answer 12

U50, 488-H

Question 13

Which protein is recruited on action of mu opioid receptors?

Answer 13

Beta arrestin

Question 14

What does beta-arrestin allow?

Answer 14

Communication between opioid receptors and other signal transduction pathways

And receptor endocytosis

Question 15

Which other pathways do mu opioids communicate with to exert negative effects?

Answer 15

AKT

c-Src

Question 16

What does prolonged activation of opioids lead to?

Answer 16

Receptor phosphorylation and b-arr-2 recruitment

Question 17

What is the likely process which leads to opioid analgesic tolerance?

Answer 17

Something to do with beta-arrestin action downstream - potentially c-Src related

Prev thought to be receptor endocytosis, but agonists which don’t cause endocytosis also seem to cause tolerance so its probs not that

Question 18

Why do we think b-arr-2 is involved in tolerance?

Answer 18

Repeated morphine administration decreases the %MPE in WT mice

But not in b-arr-2 KO mice

Question 19

Which other conditions have mu opioid receptors been involved in?

Answer 19

Binge eating

Gambling

Question 20

Why do we think mu opioid receptors are involved in drug addiction?

Answer 20

Condition place preference to morphine much weaker in mu KO mice than wild type

Question 21

Mu opioid receptors are probs the main receptor through which morphine acts

T/F

Answer 21

T

Mu KO mice display no known effects of opioids (good or bad)

Question 22

Is dopamine involved in opioid addiction? Why?

Answer 22

Probs
D2 KO mice don’t establish as strong a conditioned place preference for morphine, and is slower?
(Maldonado et al 1997)

TH KO mice don’t display increased locomotion on morphine administration. This is restored by L-dopa
Hnasko et al 2005

Question 23

What is dopamine synthesised by?

Answer 23

Tyrosine hydroxylase (TH)

Question 24

What evidence is there to show that addiction may be able to form in the absence of DA ?

Answer 24

TH KO mice still exhibit morphine reward