NEURO PHARMA ESSAY QUESTIONS WITH
ANSWERS ASSURED SUCCEED
Alcohol
• Describe how acute alcohol, working on the glutamatergic system at the synaptic
level, can impair memory formation. There are two modes of action; for each mode of
action, describe why there would be memory impairment.
EXPERIMENT: Rat swims around a pool and tries to find a platform (with objects around to
help the rat locate). When given alcohol, rats cannot find the platform as quickly. When given
ethanol it is shown that there is 50% memory loss in the rat due to ethanol when compared to
consumption of water when dealing with time vs. % of Day 1 latency.
When comparing time and amount of glutamate, there is a 20% decrease in memory function
due to ethanol shown within the hippocampus when using water as a control. (High glutamate
levels when taking water but decrease 20% when taking ethanol).
How can the effects of chronic alcohol on GABA and glutamate systems be related to
tolerance and signs of withdrawal?
Very high concentration blocks the chloride current thus increasing glutamate. An increase in
glutamate leads to seizure activity = causing hyperexcitability.
Initially, ethanol facilitates GABA transmission leading to reduced glutamate release but
chronically, GABA transmission is lost leading to increased glutamate release.
Repeated exposure to ethanol reduces GABAA-mediated chloride flux thus lack of inhibitory
control on glutamatergic neurons = seizure activity, cell death…
Repeated use of alcohol (binging) results in up-regulation of NMDA receptors. Glutamate
release that is normally reduced by alcohol increases with binge drinking patterns.
Explain the metabolic pathways of alcohol and how you could manipulate this pathway to
reduce alcohol intake.
Stomach >Small Intestine >Portal Vein --> Liver (First-pass metabolism); 95% is metabolized
by the liver, 5% is excreted by lungs (measured by breathalyzer) >Drug conjugate to heart and
systematic circulation --> Brain
Food in the stomach delays the movement of alcohol into the small intestine.
In the liver, Ethanol gets converted to acetaldehyde by alcohol dehydrogenase (ADH).
, Acetaldehyde gets converted to acetate by aldehyde dehydrogenase (ALDH).
NOTE: Acetaldehyde is very toxic, 10% of Asians have genes that encode for inactive ALDH
leading to the build-up of acetaldehyde causing symptoms of a hangover.
NOTE: Both ADH and ALDH have polymorphisms that affect the rate at which acetaldehyde is
generated and metabolized.
Reducing alcohol intake could happen by inhibiting acetaldehyde dehydrogenase from breaking
down acetaldehyde >produces negative effects like headache, nausea
Nicotine
Describe the 3 ways in which smoking cigarettes can increase dopamine levels. For each
mechanism, explain where specifically (part of cell/brain region) it is having its effect
(e.g.axon hillock - brainstem; autoreceptor-dorsal raphe) and what receptor/enzyme it is
working on.
Nicotine works by activating nicotinic cholinergic receptors (nAChRs) found in the ganglia of
the autonomic nervous system.
Nicotine binds with presynaptic receptors thereby increasing the influx of cellular calcium
leading to neurotransmitter release from the terminal. This neurotransmitter can be many but
dopamine is the main focus.
Nicotine acts on the brainstem, thalamic, striatal, and cortical sites.
The primary pathway for nicotine reinforcement is the mesolimbic dopamine tract.
Nicotine stimulates burst firing in the VTA neurons resulting in enhanced dopamine
release in the nucleus accumbens.
Chronic exposure to nicotine creates the up-regulation of high-affinity nicotinic receptor
expression within in the prefrontal cortex.
Tobacco smoke contains other compounds that inhibit monoamine oxidase (MAO).
Increase of Calcium ions
Describe the composition of a typical cigarette and explain how the psychoactive component
is delivered to the body and brain. Where in the brain does nicotine exert its primary effects?
Composition: Tiny particles called tar, a complex mixture of hydrocarbons (can be carcinogenic).
Nicotine is the psychoactive component and is delivered by inhalation.
, Nicotine readily passes through the absorbent surface of the lungs to the bloodstream.
It is absorbed in a lesser amount through the mouth and nostrils when tobacco is
chewed or snorted as snuff.
70-80% of nicotine is metabolized by the liver by cytochrome P450 to the nicotine iminium ion.
This metabolite can be oxidized by aldehyde oxidase to cotinine which is a non-psychoactive
form.
Cotinine does not bind to nAChRs but does have a half-life of 19hrs. The nicotine iminium ion
can be converted back to nicotine via CYP2A6 which can then go to the brain.
Nicotine exerts its primary effects in the brain, more specifically brainstem, thalamic, striatal,
and cortical sites.
• Explain how nicotine can enhance cognitive function by providing 1) a mechanism of
action,
2) what cognitive and 3) evidence to support this.
Nicotine works by activating nicotinic cholinergic receptors (nAChRs) found in the ganglia of
the autonomic nervous system, one of the two subtypes of the ACh receptor. Because ACh
plays an important role in cognitive functioning, several studies have looked at the effects of
nicotine on cognitive functioning.
ACh terminals make excitatory contacts with glutamate-containing pyramidal cells and granule
cells which make up the main excitatory network of the hippocampus.
EXPERIMENT: Nicotine is given to non-smokers showed a significant decrease in errors of
omission and an increase in a measure of composite attention.
Caffeine
• Explain the distinction between the direct and indirect pathways of the
caudate putamen. What pathway and receptor is caffeine hypothesized to
interfere with?
Indirect: If activity is high in the excitatory pathway, the thalamus will be inhibited reducing
cortical input and decreasing movement.
Direct: If activity in the inhibitory pathway is high, the thalamus will be free to excite the cortex,
amplifying movement.
Caffeine is said to interfere with all G-coupled receptors but mostly with A2A (Gs) and A1
ANSWERS ASSURED SUCCEED
Alcohol
• Describe how acute alcohol, working on the glutamatergic system at the synaptic
level, can impair memory formation. There are two modes of action; for each mode of
action, describe why there would be memory impairment.
EXPERIMENT: Rat swims around a pool and tries to find a platform (with objects around to
help the rat locate). When given alcohol, rats cannot find the platform as quickly. When given
ethanol it is shown that there is 50% memory loss in the rat due to ethanol when compared to
consumption of water when dealing with time vs. % of Day 1 latency.
When comparing time and amount of glutamate, there is a 20% decrease in memory function
due to ethanol shown within the hippocampus when using water as a control. (High glutamate
levels when taking water but decrease 20% when taking ethanol).
How can the effects of chronic alcohol on GABA and glutamate systems be related to
tolerance and signs of withdrawal?
Very high concentration blocks the chloride current thus increasing glutamate. An increase in
glutamate leads to seizure activity = causing hyperexcitability.
Initially, ethanol facilitates GABA transmission leading to reduced glutamate release but
chronically, GABA transmission is lost leading to increased glutamate release.
Repeated exposure to ethanol reduces GABAA-mediated chloride flux thus lack of inhibitory
control on glutamatergic neurons = seizure activity, cell death…
Repeated use of alcohol (binging) results in up-regulation of NMDA receptors. Glutamate
release that is normally reduced by alcohol increases with binge drinking patterns.
Explain the metabolic pathways of alcohol and how you could manipulate this pathway to
reduce alcohol intake.
Stomach >Small Intestine >Portal Vein --> Liver (First-pass metabolism); 95% is metabolized
by the liver, 5% is excreted by lungs (measured by breathalyzer) >Drug conjugate to heart and
systematic circulation --> Brain
Food in the stomach delays the movement of alcohol into the small intestine.
In the liver, Ethanol gets converted to acetaldehyde by alcohol dehydrogenase (ADH).
, Acetaldehyde gets converted to acetate by aldehyde dehydrogenase (ALDH).
NOTE: Acetaldehyde is very toxic, 10% of Asians have genes that encode for inactive ALDH
leading to the build-up of acetaldehyde causing symptoms of a hangover.
NOTE: Both ADH and ALDH have polymorphisms that affect the rate at which acetaldehyde is
generated and metabolized.
Reducing alcohol intake could happen by inhibiting acetaldehyde dehydrogenase from breaking
down acetaldehyde >produces negative effects like headache, nausea
Nicotine
Describe the 3 ways in which smoking cigarettes can increase dopamine levels. For each
mechanism, explain where specifically (part of cell/brain region) it is having its effect
(e.g.axon hillock - brainstem; autoreceptor-dorsal raphe) and what receptor/enzyme it is
working on.
Nicotine works by activating nicotinic cholinergic receptors (nAChRs) found in the ganglia of
the autonomic nervous system.
Nicotine binds with presynaptic receptors thereby increasing the influx of cellular calcium
leading to neurotransmitter release from the terminal. This neurotransmitter can be many but
dopamine is the main focus.
Nicotine acts on the brainstem, thalamic, striatal, and cortical sites.
The primary pathway for nicotine reinforcement is the mesolimbic dopamine tract.
Nicotine stimulates burst firing in the VTA neurons resulting in enhanced dopamine
release in the nucleus accumbens.
Chronic exposure to nicotine creates the up-regulation of high-affinity nicotinic receptor
expression within in the prefrontal cortex.
Tobacco smoke contains other compounds that inhibit monoamine oxidase (MAO).
Increase of Calcium ions
Describe the composition of a typical cigarette and explain how the psychoactive component
is delivered to the body and brain. Where in the brain does nicotine exert its primary effects?
Composition: Tiny particles called tar, a complex mixture of hydrocarbons (can be carcinogenic).
Nicotine is the psychoactive component and is delivered by inhalation.
, Nicotine readily passes through the absorbent surface of the lungs to the bloodstream.
It is absorbed in a lesser amount through the mouth and nostrils when tobacco is
chewed or snorted as snuff.
70-80% of nicotine is metabolized by the liver by cytochrome P450 to the nicotine iminium ion.
This metabolite can be oxidized by aldehyde oxidase to cotinine which is a non-psychoactive
form.
Cotinine does not bind to nAChRs but does have a half-life of 19hrs. The nicotine iminium ion
can be converted back to nicotine via CYP2A6 which can then go to the brain.
Nicotine exerts its primary effects in the brain, more specifically brainstem, thalamic, striatal,
and cortical sites.
• Explain how nicotine can enhance cognitive function by providing 1) a mechanism of
action,
2) what cognitive and 3) evidence to support this.
Nicotine works by activating nicotinic cholinergic receptors (nAChRs) found in the ganglia of
the autonomic nervous system, one of the two subtypes of the ACh receptor. Because ACh
plays an important role in cognitive functioning, several studies have looked at the effects of
nicotine on cognitive functioning.
ACh terminals make excitatory contacts with glutamate-containing pyramidal cells and granule
cells which make up the main excitatory network of the hippocampus.
EXPERIMENT: Nicotine is given to non-smokers showed a significant decrease in errors of
omission and an increase in a measure of composite attention.
Caffeine
• Explain the distinction between the direct and indirect pathways of the
caudate putamen. What pathway and receptor is caffeine hypothesized to
interfere with?
Indirect: If activity is high in the excitatory pathway, the thalamus will be inhibited reducing
cortical input and decreasing movement.
Direct: If activity in the inhibitory pathway is high, the thalamus will be free to excite the cortex,
amplifying movement.
Caffeine is said to interfere with all G-coupled receptors but mostly with A2A (Gs) and A1
