Alcohol
Opioids
Cocaine/Amphetamines
Nicotine/MJ
MJ/Hallucinogens
100
Is alcohol easily soluble in lipid or water? Can it get past the BBB?
Both! and yes!
100
Alongside the effects of opiates on the nervous system(pain relief and sedation), what other bodily system could it dangerously impair?
Respiration is dangerously impaired due to morphine's action on the brain stem respiratory center.
100
Amphetamines structurally resemble what neurotransmitter(s)?
Dopamine and norepinephrine. All have a ring-carbon-nitrogen chain.
100
Fastest route of administration for nicotine?
After inhalation it reaches high levels in the brain within 10-20 seconds, thus being even faster than an intravenous administration.
(Don't forget this exception for nicotine)
100
True or False: Psilocybin is the active agent in magic mushrooms.
FALSE! After ingestion, psilocybin is converted to psilocin, the actual psychoactive agent.
200
Ethanol binds to GABA-A receptors. However, repeated exposure of alcohol to these receptors reduces mediated influx of an ion. Name this ion.
Ethanol binds to GABAA receptors and increases Cl- influx. Tolerance reduces GABAA mediated Cl- influx.
200
Which of these is not a form of cellular inhibition caused by endogenous opioids?
• Opening K+ channels
• Closing Ca2+ channels
• Reducing release of co-localized neurotransmitter
• Closing Cl- channels
• Closing Cl- channels
1. Post-synaptic inhibition: Opioid receptors on the postsynaptic membrane activate K+ channels leading to hyperpolarization and reduction in firing rate.
2. Axoaxonal inhibition: Receptors on axon terminal are activated, G-proteins close Ca2+ channels preventing the release of synaptic vesicles and neurotransmitter.
3. Presynaptic auto-receptor: Expressed on the axon terminal of the presynaptic neuron, binding activates g-proteins to reduce the release of neurotransmitter and decreasing firing of the post-synaptic neuron.
200
Cocaethylene is a unique metabolite formed from the combination of which 2 drugs? What property does this metabolite have as opposed to each of the individual drugs?
Cocaine plus alcohol produce a unique metabolite called cocaethylene, which has activity similar to cocaine, but a longer half-life.
200
What nAChRs are primarily responsible for the reinforcing effects of nicotine and development of dependence and addiction?
α4β2
200
Hallucinogens can be divided into 2 families. Name them and what receptor all of them are agonists for.
Serotonin-like indoleamines and Catecholamine-like phenethylamine. Every one is a full or partial 5-HT2A receptor agonist without the normal 5-HT1A inhibition.
300
Name a specific and non-specific action of alcohol on the cell.
Specific: Acts at neurotransmitter binding site, modifies gating mechanism inside channel, directly interacts with channel protein, and stimulates Gs.
Nonspecific: Disturbs relationship of protein in membrane, interacts with POLAR heads of phospholipids, and alters lipid composition.
300
What brain structure is heavily implicated in the physiological response to withdrawal?
Locus coeruleus
300
True or False: Cocaine has a higher affinity for dopamine compared to serotonin.
FALSE! The ranking from highest affinity to lowest is Serotonin>Dopamine>Norepinephrine.
300
True or False: Mallory has recently accepted a new job offer. Thus, she must undergo a drug screening in 4 weeks. She takes a THC-containing substance for medical purposes everyday, but it has never been formally prescribed to her. If she stops now, Mallory will be clear for the test.
TRUE! Despite rapid initial decline in plasma concentration, the ½ life of THC in the bloodstream is 20-30 hrs. Complete elimination from the body is much slower because of persistence in fat tissues. Urine screening tests can detect them more than 2 weeks after a single marijuana use. 4 weeks is in the clear zone.
300
PCP and ketamine play what role in regards to NMDA receptors?
They are both UNcompetitive antagonists. Uncompetitive antagonists differ from non-competitive antagonists because agonists must first activate the receptor before binding to the uncompetitive antagonist, whereas non-competitive antagonists do not compete for the same binding site as an agonist.
400
You are an emergency care doctor. A patient presents with severe flushing and an alarming heart rate after celebrating her 21st birthday with some alcohol. Which enzyme is most likely altered in activity? Are there any other probable explanations?
Aldehyde dehydrogenase. This increases acetaldehyde, which can lead to flushing, headache, and an INCREASED heart rate. Additionally, genetic differences can present the same issue. The patient could be homozygous for the inactive form of aldehyde dehydrogenase.
400
A patient is trying their best to get rid of their addiction. But they are extremely scared of the withdrawals effects that might occur. What is the best drug to start them on? How does it work?
Methadone. While Methadone is a full opioid receptor agonist, it has a slower onset and long halflife, the longer the duration of action of the opioid, the more prolonged the abstinence and the lower the intensity of the syndrome. This will mitigate withdrawal symptoms, without the rush. Appropriate for all levels of dependence.
400
Kevin and Evan are identical twin mice.
Kevin was given a cocaine IV line. After a few weeks though, he realized the same amount of drug was not hitting the same.
Evan received a single injection of cocaine once a week instead. However, he ends up finding himself looking at a random pen more and more every week even with the same dose.
What differentiates the tolerance and sensitization between them to the same drug?
Whether tolerance or sensitization occurs is a result of the pattern of drug exposure, the response that is being measured, and the time elapsed since the last dose.
400
The addition of nicotine results in activation of _____ nAChRs on _____(cell type) terminals & desensitization of non-_____ nAChRs on ______ cells.
The addition of nicotine results in activation of α7 nAChRs on Glutamatergic terminals & desensitization of non-α7 nAChRs on GABAergic cells
Increase Glu & decrease GABA = more excitability of DA neuron!!
400
Review the following statements about LSD and typical user experiences. Modify them if needed to ensure accuracy:
An LSD trip can be divided into 5 phases.
Psychological/physical dependence on LSD occurs quickly.
LSD falls under the catecholamine-like indoleamines.
LSD is a full/partial 5-HT2A agonist.
An LSD trip can be divided into four phases: (1) onset; (2) plateau; (3) peak; and (4) “come-down.”
Dependence is unlikely due to the inconsistency in effects.
LSD falls under the serotonin-like indoleamines.
TRUE! All hallucinogens are a full or partial 5-HT2A agonist.
500
Pick an experimental technique used to study alcohol consumption and name an advantage or disadvantage of your chosen method.
Injection: Allows for precise amounts of alcohol to be ingested/administered. Helps when testing a specific amount of alcohol’s correlation to ABV. Does not allow the animal to choose. Does not show behaviors towards alcohol reward or aversion. Can be dangerous being directly in the blood/ bypassing first metabolism.
Drinking: Ensures that dosage and concentration are consistent. Is rapidly absorbed into the bloodstream. Best models the way that most people introduce alcohol into their bodies. Can damage the liver, pure ethanol can have adverse effects. Mice don’t like drinking ethanol and could have metabolic differences that can confound results
EtOH vapor: It is a very fast way of administering alcohol. You can reliably release alcohol over an extended amount of time. It is not the most consistent with real consumption of alcohol. Most humans don’t inhale their alcohol.
Lever pressing: Quantifiable way to assess voluntary motivation for alcohol by measuring the amount of level presses done. There might not be a direct correlation as the mice just might press the lever for fun and not even feel the effects of alcohol. There is no control of dosing.
500
Match the receptor subtype to their endogenous ligand
Receptors: mu, delta, kappa, NOP-K
Ligand: Nociceptin/orphanin, Dynorphins, Endomorphins, Enkephalin
mu: endomorphins
delta: Enkephalin
kappa: Dynorphins
NOP-K: Nociceptin/orphanin
500
A monkey is given an antagonist targeting a protein involved in dopamine-mediated movement. Surprisingly, there is no change in its locomotor activity, which the researchers find puzzling. Which dopamine receptor(s) were the researchers most likely targeting, and how do these receptors function?
D1 receptors are required for the locomotor-stimulating effects of cocaine. D1 receptor is Gs, so stimulating, and cyclic AMP production is facilitated.
500
You are reading a genetic test for a patient with a family history of chain-smokers. The gene coding for cytochrome P450 2A6 (CYP2A6) is noticeably methylated at a high level in this patient. Thus, this enzyme is not expressed as much. What does this mean for the patient?
Most nicotine is metabolized to cotinine by the liver enzyme cytochrome P450 2A6 (CYP2A6). Some people have low CYP2A6 activity and thus reduced nicotine metabolism. They are less likely to become smokers, or if they do, they smoke fewer cigarettes. Normal levels of CYP2A6 activity and variation in a gene cluster that codes for the nicotinic cholinergic receptor contribute to smoking frequency, nicotine dependence, and risk of lung cancer.
500
Sue is unhappy with her weight. Ozempic is too expensive but she learns that rimonabant, a CB1 receptor antagonist, can also reduce the feeling of needing food. Why should she NOT use this?
CB1 receptor antagonists reduce food consumption BUT they also result in depression. Using a CB1 antagonist has been shown to produce hyperalgesia(increased pain sensitivity).