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PSYCH 478 > opioid receptors and systems > Flashcards

opioid receptors and systems Flashcards

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?

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?

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?

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

Enkephalins are selective for which receptor? How many subtypes?

A
  • DOR
  • 2 subtypes
22
Q

Dynorphines are selective for which receptor? How many subtypes?

A
  • KOR
  • 4 subtypes
23
Q

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

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?

A
  • extremely high affinity for MOR
  • at least 2 subtypes
  • not identified yet
  • contraction from endogenous morphine
25
Q

Nociceptins are selective for which receptor? How many subtypes? What is its effect?

A
  • nocicptin receptor
  • single species
  • anti-analgesic
26
Q

What are Endorphins, enkephalins, and dynorphins synthesized from?

A

pre-propeptide genes

27
Q

Endorphins are expressed from _______, which also gives rise to ______________ and ________________.

A

POMC; melanocyte stimulating hormones; ACTH

28
Q

slide 16

A
29
Q

Describe postsynaptic inhibition.

A

result from Gi signalling to adenylate cyclase and G-beta-gamma signalling to hyperpolarize K+ channels (GIRK)

30
Q

Describe axoaxonal inhibition.

A

Gi and cAMP signalling to inhibit voltage-gated Ca channels

31
Q

Describe presynaptic autoreceptors.

A

inhibit NT release

32
Q

Opioids are involved in ______________ at both the spinal level and at supraspinal sites.

A

modulating pain pathways

33
Q

What are the 2 components of pain perception. Explain.

A
  • 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
Q

Describe ascending pain pathways. Which fibers signal early pain and where do they project to? late pain?

A
  • 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
Q

review slide 20

A

go look at it

36
Q

Describe spinal sites for opioid analgesia.

A
  • opioidergic neurons in descneding modulatory pathways
  • opioidergic interneurons release endorphins to inhibit ascending projections neurons
37
Q

Describe supraspinal sites for opioid analgesia.

A

opioids function in the limbic system, thalamus , and sensory areas to modulate emotional components of pain

38
Q

Where do the most important descending pathways of pain originate in? Describe the descending pain modulation pathways.

A
  • 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
Q

What inhibits noradrenergic cell increased firing in response to pain?

A

MOR agonists

40
Q

see slide 23

A

go look

41
Q

In PET displacement studies, what do sensory pain scores correlate with?

A

correlate negatively with opioid release in the nucleus accumbens, amygdala, and thalamus

42
Q

Affective pain scores correlated _____________ with opioid release in the ______________, _________________, and ________________.

A

negatively; ACC, thalamus, nucleus accumbens

43
Q

TRUE or FALSE: endogenous opioids are only involved in early pain

A

FALSE: both early (acute) and late pain

PSYCH 478 (28 decks)

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