lecture 13 LOs Flashcards
what do opiod narcotic analgesics do
reduce pain without producing unconsciousness
what is the main ingredient in opium
morphine
what is heroin made of (chemical structure)
morphine with 2 acetyl groups added to it (making it more lipid soluble)
where are opioid receptors found in the body
in the brain (receptors found w radioligand binding) and also in the gut
what are endogenous opioid receptor subtypes
mu, delta, kappa, and the nociceptin/orphanin FQ receptor (aka NOP-R)
what type of receptors are found in the endogenous opioid system
g protein linked metabotropic receptors
mu receptor has high affinity for what
morphine
what does the regional distribution of mu mean regarding its effects
periaqueductal grey: analgesia
brain stem: cardiovascular/respiratory control, cough control, vomiting
thalamus: sensorimotor integration
NAc: feeding, positive reinforcement
where is the delta endogenous opioid found
predominantly in the forebrain structures
suggests roles in olfaction, motor integration, reinforcement, cognitive function
reduced activity causes anxiety
kappa receptors have distribution to where
striatum, amygdala, hypothalamus
may play a role in pain perception, fut motility, dysphoria
what does NOP do
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
what are endorphins
peptides that activate opioid receptors
what are endogenous opioid peptides synthesized from
larger precursor peptides then cleaved to smaller peptide transmitters
what type of amino acid sequences do propeptides have
for both endogenous opiates and other transmitters
what are two ways that opioid transmitters can be released
via long axonal projection systems, or by local circuit neurons
are endogenous opioids selective
no, they show a relative preference
what are mu receptors preferentially activated by
endorphins and somewhat by endomorphins
what are delta receptors preferentially activated by
enkephalins and endorphins
what are kappa receptors preferentially activated by
dynorphins
how do opioids inhibit neural activity via postsynaptic inhibition
receptors activate a G protein that opens K+ channels
how do opioids inhibit neural activity via axoaxonic inhibition - heteroreceptors
activate G proteins that close Ca2+ channels, reducing transmitter release
how do opioids inhibit neural activity via presyanptic autoreceptors
reduce release of a co-localized neurotransmitter
all opioid receptors are coupled to ____ that inhibit ____
G proteins, adenylyl cyclase-cAMP
some modifications can produce partial agonists, what does this do
bind to the receptor but have less biological effect
what is an example of an opioid receptor partial agonist and what does it do
buprenorphine: less potent than morphine, but also less risk of respiratory depression and dependence
what do pure antagonists do and what are examples of them
naloxone or naltexone, they prevent or reverse the effect of the opioid drug use
how does spinal cord opiates (spinal analgesia) work
opioid interneurons can inhibit pain projection neurons
what are two ways that opioids can activate descending pathways to project to the spine
direct inhibit the pain projection neurons
inhibit excitatory interneurons that synapse on pain projection neurons
opioids activate ___ pathways originating in the ___
two descending pain-inhibiting pathways, periaqueductal grey (PAG)
what is the periaqueductal grey (PAG) rich with
peptides and receptors
stimulation inducese analgesia that can be attenuated by opioid antagonists
opioid projections from PAG disinhibit what
serotonin and NE that suppress pain signals in spinal cord
opioid activity in supraspinal locations mediate what
emotional, autonomic, and/or neuroendocrine components of pain
therapeutic administration of opioids
intra-muscularly or orally, slower absorption, not as euphoric
recreational opioid administration
more rapid means like inhalation, snorting, IV
what do low/moderate doses of opioids do
pain relief, constricted pupils, drowsiness, inability to concentrate, dreamy sleep
what do high doses of opioids do
abnormal state of elation or euphoria
what pathway can opioids activate
mesolimbic DA, contributes to the opioid reinfocement
what does mu receptor activation do to DA
inhibits GABA neurons in VTA, disinhibits DA neuron firing therefore increasing DA release
what does kappa receptor activation do for DA
activation on terminals in the NAc reduces DA release
how does the tolerance development rate differ with opioids for pleasure vs constipation
pleasure: tolerance develops quickly
constipation: tolerance develops more slowly
what is the difference in the withdrawl of morphine or heroin versus methadone or burprenorphine
morphine: severe
methadone: less severe
what happens when the same opioid drug is re administered or another opioid is administered during withdrawal
reduction i nthe symptoms (this is how methadone works)
how can physical withdrawal symptoms be triggered
by opioid antagonists infused into the locus coeruleus or the PAG
how can emotional withdrawal be triggered
by infusions of antagonists into the NAc or the amygdala
what can methadone/buprenorphine (opioid agonists) by used for and what are the pros of that
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
what can naltrexone (opioid antagonist) be used for and what are the pros of it
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
