Opioids Flashcards
What is opium?
The product of heroin metabolism
Diacetyl-morphine (diamorphine)
What are the endogenous opioids?
Beta-endorphins
Enkephalins
What is the function of the opioid system?
Provide reward for pro-survival activities
Provide defence against pain
How do opioids produce a pleasure response?
Inhibits the GABA mediates IPSCs in the post-synaptic dopamine neuron
Inhibits APs in the presynaptic GABA neuron
Overall —> more DA
Describe the structure of the opioid receptor
7 membrane spanning domains which interact with intracellular G proteins
What are the types of opioid receptor?
Mu
Delta
Kappa
(NOP not a true receptor)
Which gene codes for mu opioid receptors?
OPRM1
Which gene codes for delta opioid receptors?
OPRD1
Which gene codes for kappa opioid receptors?
OPRK1
What is the main selective agonist of mu opioid receptors?
DAMGO
What is a selective agonist of delta receptors?
DPDPE
What is the selective agonist of kappa opioid receptors?
U50, 488-H
Which protein is recruited on action of mu opioid receptors?
Beta arrestin
What does beta-arrestin allow?
Communication between opioid receptors and other signal transduction pathways
And receptor endocytosis
Which other pathways do mu opioids communicate with to exert negative effects?
AKT
c-Src
What does prolonged activation of opioids lead to?
Receptor phosphorylation and b-arr-2 recruitment
What is the likely process which leads to opioid analgesic tolerance?
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
Why do we think b-arr-2 is involved in tolerance?
Repeated morphine administration decreases the %MPE in WT mice
But not in b-arr-2 KO mice
Which other conditions have mu opioid receptors been involved in?
Binge eating
Gambling
Why do we think mu opioid receptors are involved in drug addiction?
Condition place preference to morphine much weaker in mu KO mice than wild type
Mu opioid receptors are probs the main receptor through which morphine acts
T/F
T
Mu KO mice display no known effects of opioids (good or bad)
Is dopamine involved in opioid addiction? Why?
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
What is dopamine synthesised by?
Tyrosine hydroxylase (TH)
What evidence is there to show that addiction may be able to form in the absence of DA ?
TH KO mice still exhibit morphine reward
