lecture 13 LOs

Question 1

what do opiod narcotic analgesics do

Answer 1

reduce pain without producing unconsciousness

Question 2

what is the main ingredient in opium

Answer 2

morphine

Question 3

what is heroin made of (chemical structure)

Answer 3

morphine with 2 acetyl groups added to it (making it more lipid soluble)

Question 4

where are opioid receptors found in the body

Answer 4

in the brain (receptors found w radioligand binding) and also in the gut

Question 4

what are endogenous opioid receptor subtypes

Answer 4

mu, delta, kappa, and the nociceptin/orphanin FQ receptor (aka NOP-R)

Question 5

what type of receptors are found in the endogenous opioid system

Answer 5

g protein linked metabotropic receptors

Question 6

mu receptor has high affinity for what

Answer 6

morphine

Question 7

what does the regional distribution of mu mean regarding its effects

Answer 7

periaqueductal grey: analgesia
brain stem: cardiovascular/respiratory control, cough control, vomiting
thalamus: sensorimotor integration
NAc: feeding, positive reinforcement

Question 8

where is the delta endogenous opioid found

Answer 8

predominantly in the forebrain structures
suggests roles in olfaction, motor integration, reinforcement, cognitive function
reduced activity causes anxiety

Question 9

kappa receptors have distribution to where

Answer 9

striatum, amygdala, hypothalamus
may play a role in pain perception, fut motility, dysphoria

Question 10

what does NOP do

Answer 10

does not bind to opioid drugs
role in analgesia, feeding, learning, motor function, reward and neuroendocrine regulation
NOP agonists have minimal abuse potential and cause less respiratory depression

Question 11

what are endorphins

Answer 11

peptides that activate opioid receptors

Question 12

what are endogenous opioid peptides synthesized from

Answer 12

larger precursor peptides then cleaved to smaller peptide transmitters

Question 13

what type of amino acid sequences do propeptides have

Answer 13

for both endogenous opiates and other transmitters

Question 14

what are two ways that opioid transmitters can be released

Answer 14

via long axonal projection systems, or by local circuit neurons

Question 15

are endogenous opioids selective

Answer 15

no, they show a relative preference

Question 16

what are mu receptors preferentially activated by

Answer 16

endorphins and somewhat by endomorphins

Question 17

what are delta receptors preferentially activated by

Answer 17

enkephalins and endorphins

Question 18

what are kappa receptors preferentially activated by

Answer 18

dynorphins

Question 19

how do opioids inhibit neural activity via postsynaptic inhibition

Answer 19

receptors activate a G protein that opens K+ channels

Question 20

how do opioids inhibit neural activity via axoaxonic inhibition - heteroreceptors

Answer 20

activate G proteins that close Ca2+ channels, reducing transmitter release

Question 21

how do opioids inhibit neural activity via presyanptic autoreceptors

Answer 21

reduce release of a co-localized neurotransmitter

Question 22

all opioid receptors are coupled to ____ that inhibit ____

Answer 22

G proteins, adenylyl cyclase-cAMP

Question 23

some modifications can produce partial agonists, what does this do

Answer 23

bind to the receptor but have less biological effect

Question 24

what is an example of an opioid receptor partial agonist and what does it do

Answer 24

buprenorphine: less potent than morphine, but also less risk of respiratory depression and dependence

Question 25

what do pure antagonists do and what are examples of them

Answer 25

naloxone or naltexone, they prevent or reverse the effect of the opioid drug use

Question 26

how does spinal cord opiates (spinal analgesia) work

Answer 26

opioid interneurons can inhibit pain projection neurons

Question 27

what are two ways that opioids can activate descending pathways to project to the spine

Answer 27

direct inhibit the pain projection neurons inhibit excitatory interneurons that synapse on pain projection neurons

Question 28

opioids activate ___ pathways originating in the ___

Answer 28

two descending pain-inhibiting pathways, periaqueductal grey (PAG)

Question 29

what is the periaqueductal grey (PAG) rich with

Answer 29

peptides and receptors stimulation inducese analgesia that can be attenuated by opioid antagonists

Question 30

opioid projections from PAG disinhibit what

Answer 30

serotonin and NE that suppress pain signals in spinal cord

Question 31

opioid activity in supraspinal locations mediate what

Answer 31

emotional, autonomic, and/or neuroendocrine components of pain

Question 32

therapeutic administration of opioids

Answer 32

intra-muscularly or orally, slower absorption, not as euphoric

Question 33

recreational opioid administration

Answer 33

more rapid means like inhalation, snorting, IV

Question 34

what do low/moderate doses of opioids do

Answer 34

pain relief, constricted pupils, drowsiness, inability to concentrate, dreamy sleep

Question 35

what do high doses of opioids do

Answer 35

abnormal state of elation or euphoria

Question 36

what pathway can opioids activate

Answer 36

mesolimbic DA, contributes to the opioid reinfocement

Question 37

what does mu receptor activation do to DA

Answer 37

inhibits GABA neurons in VTA, disinhibits DA neuron firing therefore increasing DA release

Question 38

what does kappa receptor activation do for DA

Answer 38

activation on terminals in the NAc reduces DA release

Question 39

how does the tolerance development rate differ with opioids for pleasure vs constipation

Answer 39

pleasure: tolerance develops quickly constipation: tolerance develops more slowly

Question 40

what is the difference in the withdrawl of morphine or heroin versus methadone or burprenorphine

Answer 40

morphine: severe methadone: less severe

Question 41

what happens when the same opioid drug is re administered or another opioid is administered during withdrawal

Answer 41

reduction i nthe symptoms (this is how methadone works)

Question 42

how can physical withdrawal symptoms be triggered

Answer 42

by opioid antagonists infused into the locus coeruleus or the PAG

Question 43

how can emotional withdrawal be triggered

Answer 43

by infusions of antagonists into the NAc or the amygdala

Question 44

what can methadone/buprenorphine (opioid agonists) by used for and what are the pros of that

Answer 44

maintenance/replacement treatments prevents severe withdrawal symptoms and reduces cravings cross tolerance develops so the euphoric effects of the initial drug are reduced can produce a high if injected

Question 45

what can naltrexone (opioid antagonist) be used for and what are the pros of it

Answer 45

longer lasting naloxone, orally active only effective for highly motivated individuals (bc drug craving is not eliminated) less motivated addicts stop treatment and return to drug use