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PSYCH 478 > opioid receptors and systems > Flashcards

opioid receptors and systems Flashcards

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1
Q

What effects are difficult to directly measure in lab based assays? Why?

A
  • analgesic
  • ethical constraints with animals
  • human trials confounded by subjectivity
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2
Q

We know opioids are potent modulators of _______________.

A

GI mobility

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3
Q

Investigators developed a GI based assay to measure ____________.

A

the potency of opioids

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4
Q

Application of hydraulic pressure stimulates what in an ex vivo preparation of what animal? What does this assess?

A
  • stimulates ileum peristaltic reflex in guinea pig ileum
  • assess opioid potencyand endogenous opiod release
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5
Q

Which endogenous opioid reversibly inhibits the ileum peristaltic reflex?

A

morphine

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6
Q

Which drug rapidly restores ileum peristaltic reflex?

A

naloxone (opioid antagonist)

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7
Q

Potency in the guinea pig ileum strongly correlates with ___________ in humans.

A

analgesic potency

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8
Q

How were opioid receptors first identified? What did it reveal about opioid binding?

A
  • radiolabelled naloxone (opioid antagonist)
  • opioid binding was reversible, saturable, and high affinity
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9
Q

Opioid receptor binding by the radioligand assay was shown to correlate with __________.

A

the potency of opioids in the guinea pig ileum bioassay

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10
Q

Demonstration of the binding of radioligands in the _____ brain highlights sites of opioid reeptor. High binding observed in the ________, __________, _______, ___________, and ____________.

A

rat; striatum, locus coeruleus, thalamus, raphe nuclei, and periaqueductal gray

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11
Q

TRUE or FALSE: opioid receptors are ionotropic

A

FALSE: G-protein coupled (Gi)

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12
Q

What are the 4 main opioid receptor sybtypes?

A

δ (delta) – DOR / OP1
κ (kappa) – KOR / OP2
μ (mu) – MOR / OP3
Nociceptin – NOP / OP4

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13
Q

see slide 11 diagram for mu delta and kappa distribution in the brain

A

go look at it

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14
Q

Answer the following for MOR:
- high affinity for?
- expression in thalamus, PAG, median raphe suggest?
- expression in nucleus accumbens suggest?
- expression in brainstem suggest?

A
  • high affinity for morphine
  • analgesia
  • reinforcement
  • resp depression, cough suppression, vomit reflex
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15
Q

TRUE or FALSE: KOR has similar expression as MOR but more restricted

A

FALSE: DOR expression similar to MOR but more restricted

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16
Q

TRUE or FALSE: DOR is sensitive to morphine

A

FALSE: not sensitive

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17
Q

What does DOR have roles in?

A

olfaction, motor integration, reinforcement, analgesia

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18
Q

Answer the following for KOR:
- what kind of expression pattern?
- high affinity for?
- expressed in?
- regulate what?
- additional roles in?

Study These Flashcards
A
  • distinct expression pattern
  • ketocyclazocine
  • striatum, amygdala, hypothalamys, pituitary
  • pain perception, gut motility, dysphoria
  • water balance, feeding, temp control, neuroendocrine function
19
Q

Where is nociceptin receptor expressed? What are the roles?

Study These Flashcards
A
  • Expressed in amygdala, hippocampus, hypothalamus, and spinal cord
  • Roles in anxiety, depression, appetite, and development of tolerance to μ-opioid agonists
20
Q

ketocyclazocine binds to what receptor? what is it and what does it do?

Study These Flashcards
A
  • Synthetic opioid that is hallucinogenic and induces dysphoria
  • binds to KOR
21
Q

Enkephalins are selective for which receptor? How many subtypes?

Study These Flashcards
A
  • DOR
  • 2 subtypes
22
Q

Dynorphines are selective for which receptor? How many subtypes?

Study These Flashcards
A
  • KOR
  • 4 subtypes
23
Q

Endorphins are selective for which receptor? How many subtypes? What are they contracted from?

Study These Flashcards
A
  • MOR
  • 5 subtypes
  • contraction from endogenous MORPHINE
24
Q

Endomorphins are selective for which receptor? How many subtypes? Is the gene or prepeptide identified yet? What is it contracted from?

Study These Flashcards
A
  • extremely high affinity for MOR
  • at least 2 subtypes
  • not identified yet
  • contraction from endogenous morphine
25
Nociceptins are selective for which receptor? How many subtypes? What is its effect?
- nocicptin receptor - single species - anti-analgesic
26
What are Endorphins, enkephalins, and dynorphins synthesized from?
pre-propeptide genes
27
Endorphins are expressed from _______, which also gives rise to ______________ and ________________.
POMC; melanocyte stimulating hormones; ACTH
28
slide 16
29
Describe postsynaptic inhibition.
result from Gi signalling to adenylate cyclase and G-beta-gamma signalling to hyperpolarize K+ channels (GIRK)
30
Describe axoaxonal inhibition.
Gi and cAMP signalling to inhibit voltage-gated Ca channels
31
Describe presynaptic autoreceptors.
inhibit NT release
32
Opioids are involved in ______________ at both the spinal level and at supraspinal sites.
modulating pain pathways
33
What are the 2 components of pain perception. Explain.
- early pain - immediate SENSORY component signalling stimulus LOCATION to cause withdrawal or escape from stimulus - late pain - signals a strong EMOTION component, the unpleasantness of pain sensation – prolongs sensation of pain to focus behaviours to limit further damage and aid recovery
34
Describe ascending pain pathways. Which fibers signal early pain and where do they project to? late pain?
- sensory neurons in DRG transmit signals in dorsal horn to ascending pathways - early pain = A-delta fibers to thalamus and somatosensory cortex --> localize info on pain - late pain = C fibers to thalamus and limbic system (hypothalamus, amygdala, ACC)
35
review slide 20
go look at it
36
Describe spinal sites for opioid analgesia.
- opioidergic neurons in descneding modulatory pathways - opioidergic interneurons release endorphins to inhibit ascending projections neurons
37
Describe supraspinal sites for opioid analgesia.
opioids function in the limbic system, thalamus , and sensory areas to modulate emotional components of pain
38
Where do the most important descending pathways of pain originate in? Describe the descending pain modulation pathways.
- most important in PAG - PAG neurons --> raphe nuclei --> serotonergic projections inhibit input to pain afferents - PAG --> LC --> noradrenergic projetions incresae firing in respnse to pain
39
What inhibits noradrenergic cell increased firing in response to pain?
MOR agonists
40
see slide 23
go look
41
In PET displacement studies, what do sensory pain scores correlate with?
correlate negatively with opioid release in the nucleus accumbens, amygdala, and thalamus
42
Affective pain scores correlated _____________ with opioid release in the ______________, _________________, and ________________.
negatively; ACC, thalamus, nucleus accumbens
43
TRUE or FALSE: endogenous opioids are only involved in early pain
FALSE: both early (acute) and late pain

PSYCH 478 (28 decks)

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