Transcript
Alcohol and Opioids (55pts)
What are the acute effects of alcohol on (3pts):
Acute effects = sudden onset
Glutamate = major excitatory neurotransmitter
GABA = major inhibitory amino acid neurotransmitter
Dopamine = motivation
Glutamate : inhibits NMDA receptors – decreases effects -- sedative (p.238)
Note: NMDA receptors mediate associative learning
GABA : alcohol binds, increased intake of Cl –increases effects of
intoxication (p.329)
Note: high concentration associated with greater intoxication
Dopamine: increased dopaminergic transmission in mesolimbic pathway
Note: pathway begins in the VTA of midbrain to limbic system to nucleus accumbus
What are the chronic effects of alcohol on (2pts):
Chronic effects = long lasting
Glutamate : upregulation of NMDA receptors in cerebral cortex and hippocampus in response to glutamate activity (p.328)
During withdrawal: excess Calcium influx leads to cell death
GABA : reduces GABA mediated Cl- flux, increases animal sensitivity to seizure-inducing doses of GABA antagonist bicuculline
associated to tolerance, some signs of withdrawal (hyperexcitability, seizures, and tremors) because of reduced GABA-mediated inhibition
(p.329-330)
Following prolonged exposure to EtOH, compensatory changes occur in the NMDA receptor. The changes are beautifully represented in panels A-C below. Using the text boxes supplied, please explain what is happening in each of these panels (15pts) : alcohol = negative allosteric inhibitor
* glutamate binds to receptor- without there will be no release of Ca2+
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Normal function: Ca2+ in
367665047625Ion movement: Alcohol binds to NMDA receptor, decreasing Ca intake (decreasing receptor efficiency)
Behavioral: intoxication, poor movement, cognitive deficits, euphoria
00Ion movement: Alcohol binds to NMDA receptor, decreasing Ca intake (decreasing receptor efficiency)
Behavioral: intoxication, poor movement, cognitive deficits, euphoria
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5pts
371968950307B. In order to regain excitatory function, system engages in neuroadaptation –upregulates NMDA receptors to increase expression on membranes –to get closer to 100% baseline that CNS wants -(upregulate to gain tolerance)
Behavioral: better” intoxicated motor movements” ..develop tolerance to subjective effects, not ass euphoric…there will still be cognitive deficits
00B. In order to regain excitatory function, system engages in neuroadaptation –upregulates NMDA receptors to increase expression on membranes –to get closer to 100% baseline that CNS wants -(upregulate to gain tolerance)
Behavioral: better” intoxicated motor movements” ..develop tolerance to subjective effects, not ass euphoric…there will still be cognitive deficits
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5pts
3719689167428C. NMDA receptors function at 100% -- each receptor functioning ---hyperexcitability (overexcitation) because of additional receptors that are active at full potential
Ion movement: increase in Ca2+
Symptoms: seizures
00C. NMDA receptors function at 100% -- each receptor functioning ---hyperexcitability (overexcitation) because of additional receptors that are active at full potential
Ion movement: increase in Ca2+
Symptoms: seizures
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5pts
Opioids inhibit nerve activity in several different ways, depending on where the receptors are located. Please explain the effects of the following, in detail:
Slide 36 Ch. 11
Postsynaptic inhibition (5pts):
Receptors activate a G-protein, opens K+ channels
Reducing firing rate of postsynaptic cell
Axoaxonic Inhibition (5pts):
Receptors activate G proteins, close Ca2+ channels
Reducing the release of neurotransmitter
Presynaptic autoreceptors (5pts):
Activate G proteins
Reduce release of co-localized neurotransmitter
Peptides
Where are they synthesized (1pt)?
In the soma
How and where are they liberated (1pt)?
Released at the terminal (similar to neurotransmitters) – require more Calcium and neuroactivity
List the 3 classic opioid receptors and the ligand for each type (3pts):
? (mu)- high affinity for morphine and related opioid drugs (p. 358)
Endomorphin
Endorphin
? (delta)- reinforcement, cognition, olfaction, motor integration
Enkephalin
Endorphins
? (kappa)-
Dynorphin
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Using the diagram above (10pts):
EXAMPLE:
Explain how activation of the GABA neuron in the VTA affects DA release in the NAcc (independent of the possible influence of ?-endorphin or dynorphin):
Increased activity of the GABA neuron would activate ionotropic GABA receptors on the DA neuron that terminates in the NAcc. This would allow Cl- to enter the cell, which would hyperpolarize the cell membrane and which would decrease DA release in the NAcc.
What type of inhibition is described in the diagram (see question 4)?
presynaptic
What happens to GABA release when ?-endorphin is administered?
decreased
How does administration of ?-endorphin affect dopamine in the NAcc?
Increase (inhibit an inhibitor – disinhibition)
How does administration of dynorphin affect dopamine in the NAcc?
decrease
How would administration of ?-endorphin affect the threshold for electrical self-stimulation?
Decrease
How would administration of dynorphin affect the threshold for electrical self-stimulation?
Decrease of dopamine; increase threshold
Below is a graph showing rate of responding in an electrical self-stimulation task. Which option would represent data for an animal (5pts):
That is drug naïve and received a single dose of heroin. Explain your selection.
Option A: lower rate – increase of dopamine in NAcc –threshold for electrical self-stimulation
decreases
That is heroin dependent and received a single dose of naloxone. Explain your selection
Option B: if given naloxone, decreases on NAcc – need to increases stimulation to achieve baseline
Opioids reduced threshold for reinforcement in electrical self-stimulation
What formic acid does
Opioid effects NE (inhibits activity) – withdrawal symptom of respiratory depression
Breakdown of alcohol:
Alcohol à acetaldehyde à acetate
Alcohol dehydrogenase aldehyde dehydrogenase (DONE BY THESE ENZYMES)
Increase of acetaldehyde makes alcohol aversive: flush face, nausea, sick
Inhibit aldehyde dehydrogenase increases sickness, nausea…
opioid addictive but are analgesics (pain killers)
drug to treat alcohol use disorder (disulfiram)
alcohol withdrawal seizures = fatal
naloxone has opposite effect of opioid – instant withdrawal
note: treatments
one question on peptides
classifications of opioids:
morphine = natural
fentanyl = synthetic
heroine = half
opioids have been around