Neuropharm notes

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+ 16819776996100 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 -3898905842000 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 -39116010033000 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 -38100015684500 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 7000521284100 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