Pharm - Introduction To CNS Pharmacology
(145).jpg "Pharm - Introduction To CNS Pharmacology - Quiz")
A person that has central nervous system disorders or ailments needs specialized care and specific medication for the various ailments. It is therefore important for a pharmacist or medical practitioner to have adequate information on the various drugs. If you just covered introduction to CNS pharmacology take the test and jog your memory.
Questions and Answers
- 1.
Which of the following statements regarding CNS drug action on synaptic potentials are correct? (Check all that apply)
- A.
A drug-induced EPSP usually makes the membrane potential less negative
- B.
An IPSP may be produced by drugs that cause opening of Cl- channels
- C.
An IPSP may be produced by drugs that cause opening of K+ channels
- D.
Most CNS drugs affect synaptic potential by activating or inhibiting NA+/K+ ATPase
- E.
All drug-induced EPSP and IPSP are very short-lasting potentials (less than 5 milliseconds)
Correct Answer(s)
A. A drug-induced EPSP usually makes the membrane potential less negative
B. An IPSP may be produced by drugs that cause opening of Cl- channels
C. An IPSP may be produced by drugs that cause opening of K+ channelsExplanation
Answer: ABC
(Katzung, pp 340, Golan pp 94)
By definition an excitatory post synaptic potential (EPSP) occurs when the membrane potential
of the postsynaptic cell becomes less negative (depolarization) so making the neuron in an
“excited” state (action potential generation is facilitated). Conversely an inhibitory postsynaptic
potential occurs when the membrane potential of the postsynaptic cell becomes more negative.
(hyperpolarization). This can happen either by increasing the negative charges inside the cell
(when Cl- channels open, Cl- enters the cell since the concentration of Cl- outside is higher
than the concentration inside) or by decreasing the positive charges inside the cell (when K+
channels open, K+ exits the cell since the concentration of K+ inside is higher than the
concentration outside ).
D) CNS drugs do not act on NA+/K+ ATPase. Actually this enzyme is very seldom a drug
target. A notable exception are cardiac glycosides, whose mechanism of action involves a
specific blockade of the enzyme.
E) EPSP and IPSP can be either fast (few milliseconds) or slow (few seconds).Rate this question:
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- 2.
CNS drugs often act on a specific neurotransmitter system. Which of the following statements correctly pairs the system with the drug class that mainly affects it?
- A.
Serotonergic system - Opioids
- B.
Cholinergic system - MAO inhibitors
- C.
Dopaminergic system - Phenothiazines
- D.
Noradrenergic system - Benzodiazepines
- E.
GABAergic system - Tricyclic antidepressants
Correct Answer
C. Dopaminergic system - pHenothiazinesExplanation
Answer: C
(Katzung, pp 463, Brunton pp 462)
Phenothiazines, butyrophenones as well as other neuroleptic drugs mainly interfere with the
dopaminergic system by blocking dopaminergic receptors. This blockade seems to underlie
both their clinical usefulness and their major adverse effects.
A) Opioids act on the endorphinergic system.
B, E) MAO inhibitors and tricyclic antidepressants mainly act on the noradrenergic and the
serotonergic systems
D) Benzodiazepines mainly act on the GABAergic systemRate this question:
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- 3.
Which of the following statements correctly matches the CNS receptor with the appropriate postreceptor mechanism? (Check all that apply)
- A.
M3 muscarinic - decreased NA+ conductance
- B.
Alpha-1 adrenergic - decreased Ca++ conductance
- C.
GABA A - increased Cl- conductance
- D.
Glycine r - decreased Cl- conductance
- E.
NMDA - decreased cation conductance
- F.
Beta-1 adrenergic - increased cAMP
- G.
5-HT3 - increased cation conductance
Correct Answer(s)
C. GABA A - increased Cl- conductance
F. Beta-1 adrenergic - increased cAMP
G. 5-HT3 - increased cation conductanceExplanation
Answer: CFG
(Katzung, pp 345, Golan pp 82)
All GABA receptors are inhibitory. Therefore they must hyperpolarize the postsynaptic
membrane. GABA A receptors do so by increasing Cl- conductance whereas GABA B receptors
do the same by increasing K+ conductance. All beta receptors are metabotropic and act by
increasing the synthesis of the second messenger cAMP. 5-HT3 receptors are mainly
excitatory. Therefore they must depolarize the postsynaptic membrane. By increasing cation
conductance Na+ can enter the cell and depolarization occurs.
A) M3 receptors are mainly excitatory. A decrease in Na+ conductance would cause an
inhibitory effect at the postsynaptic membrane. Actually activation of these receptors causes
the increased synthesis of IP3/DAG
B) Alpha-1 adrenergic receptors are excitatory. A decrease in Ca++ conductance would cause
an inhibitory effect at the postsynaptic membrane. Actually activation of these receptors
causes the increased synthesis of IP3/DAG
D) Glycine receptors are inhibitory and cause hyperpolarization of the postsynaptic membrane
by increasing, not decreasing, Cl- conductance.
E) NMDA receptors are glutamate receptors. All glutamate receptors are excitatory and cause
depolarization of the membrane by increasing, nor decreasing, cation conductance.Rate this question:
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- 4.
Some CNS depressant drugs act on a system which is critical in maintaining tonic inhibitory control on most other neuronal systems. Which of the following systems is the target for those drugs?
- A.
Noradrenergic
- B.
Serotonergic
- C.
Cholinergic
- D.
Dopaminergic
- E.
GABAergic
- F.
Endorphinergic
Correct Answer
E. GABAergicExplanation
Answer: E
(Katzung, pp 344, Brunton pp 330)
The GABAergic system is the most important inhibitory system in the brain. GABA neurons are
short interneurons located throughout the cerebrum and cerebellum, as well as in the spinal
cord.
Several CNS drugs , including anxiolytics (i.e. benzodiazepines), hypnotics (i.e. zolpidem) and
anticonvulsants (i.e. barbiturates, gabapentin, vigabatrin) exert their CNS depressant actions
by increasing, with different mechanisms, GABA activity.
A, B, C, D) All these systems are not purely inhibitory, but can exert excitatory or inhibitory
effects according to the receptors activated and the target tissue.
F) The endorphinergic system is an inhibitory system but it controls mainly pain circuits and is
not as ubiquitous as the GABAergic system.Rate this question:
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- 5.
Which the following statements related to GABA A and GABA B receptors are correct? (Check all that apply)
- A.
GABA A receptors are G-protein coupled receptors
- B.
GABA A receptors activation leads to increased Na+ conductance
- C.
GABA B receptors activation leads to IPSP
- D.
GABA A receptors blockade leads to decreased Cl- conductance
- E.
GABA B receptors blockade leads to increased K+ conductance
Correct Answer(s)
C. GABA B receptors activation leads to IPSP
D. GABA A receptors blockade leads to decreased Cl- conductanceExplanation
Answer: CD
(Katzung, pp 345, Brunton pp 330)
GABA B receptors activation leads to opening of K+ channels. This causes a hyperpolarization
of the postsynaptic membrane (K+ exits from the cell) and therefore the production of IPSP.
GABA receptors activation directly opens Cl- channels on postsynaptic membrane, so causing
an increase of Cl- conductance. GABA A receptors blockade does the opposite.
A) GABA A ionotropic, GABA B receptors are metabotropic, i.e. G-protein coupled..
B) GABA receptors do not regulate Na+ channels.
E Actually GABA B receptors activation leads to increased K+ conductance. GABA B receptors
blockade does the opposite.Rate this question:
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- 6.
A 32-year-old man, recently diagnosed with partial seizure, started a treatment with felbamate, a drug that is thought to act by blocking NMDA receptors in the brain. Which of the following systems was most likely affected by the drug?
- A.
Noradrenergic
- B.
Cholinergic
- C.
Histaminergic
- D.
Dopaminergic
- E.
Serotonergic
- F.
GABAergic
- G.
Glutamatergic
Correct Answer
G. GlutamatergicExplanation
Answer: G
(Katzung, pp 385, Brunton pp 520)
Glutamate is important excitatory neurotransmitter in the brain. Glutamate receptors include
NMDA and Ampa receptors. Drugs, like felbamate, that seem to act by blocking these
receptors can be used effectively as anticonvulsants.
A, B, C, D, E) These systems are not exclusively excitatory and therefore drugs affecting these
systems are not used as anticonvulsants.
G) The GABAergic system is a central inhibitory system. Drugs that increase the activity of this
system (like benzodiazepines and barbiturates) are currently used as anticonvulsants.Rate this question:
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- 7.
A 25-year-old woman presented to the psychiatric hospital describing a one year history of anxiety. She has been feeling tense most of the time, was often irritable and found hard to concentrate because of a great deal of distress. She was prescribed an anxiolytic drug and a cycle of psychotherapy. Which of the following neurotransmitter systems is most likely involved in the therapeutic action of the prescribed drug?
- A.
Cholinergic
- B.
Histaminergic
- C.
Glutamatergic
- D.
GABAergic
- E.
Dopaminergic
- F.
Endorphinergic
Correct Answer
D. GABAergicExplanation
Answer: D
(Katzung, pp 356, Koda-Kimble, pp 76-2)
The most commonly used anxiolytic drugs are benzodiazepines, which act by increasing the
GABAergic activity of the brain. Other drugs frequently used include buspirone (a serotonin
agonist) and SSRIs. This would indicate that the serotonergic system is also involved in
the pathogenesis of anxiety disorders.
A, B, C, E, F) these systems do not seem to play a major role in anxiety disorders.Rate this question:
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- 8.
A 25-year-old woman was brought to the Emergency Room because of a generalized tonic-clonic seizure. Her husband stated that his wife has been suffering from epilepsy since childhood, but the seizures were only partially controlled by medication. Which of the following pairs of neurotransmitters are thought to be mainly involved in seizure disorders?
- A.
GABA and serotonin
- B.
GABA and glutamate
- C.
GABA and acetylcholine
- D.
Serotonin and glutamate
- E.
Serotonin and acetylcholine
- F.
Acetylcholine and glutamate
Correct Answer
B. GABA and glutamateExplanation
Answer: B
(Katzung, pp 380, Golan, pp 194)
Epilepsy is a chronic recurrent disorder of cerebral function that may be characterized by
repeated seizures. The essence of epilepsy is probably a chronic low seizure threshold which
can be due to several mechanisms. A leading mechanism postulates that the cause of seizures
is either the attenuation of pre and/or postsynaptic inhibition (mainly due to a genetic or
postpathologic hypofunction of GABA neurons) or an increased effectiveness of excitatory
synapses (mainly due to a genetic or postpathologic hyperfunction of glutamate neurons).
A, C, D, E, F) (see explanation above)Rate this question:
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- 9.
A 34-year-old man who is a heavy smoker started a medical assisted program to quit smoking. Therapy included the administration of clonidine, an agonist at alpha-2 presynaptic receptors which is believed to act mainly on noradrenergic neurons in the brain. Which of the following areas of the brain is the richest in noradrenergic neurons?
- A.
Median Raphe Nucleus
- B.
Stria Terminalis
- C.
Locus Ceruleus
- D.
Substantia Nigra
- E.
Thalamus
Correct Answer
C. Locus CeruleusExplanation
Answer: C
(Katzung, pp 520, Brunton, pp 452)
Most noradrenergic neurons in the brain are found in the locus ceruleus, a bluish area on each
side of the median eminence of the brain stem. Locus ceruleus sends a particularly large
number of projections to the amygdala and hippocampus, where norepinephrine release is
thought to mediate emotion and memory formation. Another brain region which is rich in
noradrenergic neurons is the lateral tegmental area of the reticular formation.
Clonidine activates presynaptic alpha-2 receptors located on noradrenergic terminals and this
decreases norepinephrine release from those terminals. It seems that this reduction of central
adrenergic activity is the basis of the therapeutic effect of the drug in case of withdrawal from
addicting drugs, including nicotine and opioids.Rate this question:
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- 10.
A 23-year-old woman presented to his physician complaining of a distressing and behavior. For the past months she has experienced an irresistible urge to check that everything was in a certain order at home and found hard to get out of the house because she needed to control that the door was locked again and again. She admitted that she had an irrational fear that things were not perfect. Which of the following neurotransmitter has been most consistently implicated in this disorder?
- A.
Acetylcholine
- B.
Norepinephrine
- C.
GABA
- D.
Serotonin
- E.
Glutamate
Correct Answer
D. SerotoninExplanation
Answer: D
(Katzung, pp 490, Koda-Kimble, pp 76-38)
The patient is most likely suffering from an obsessive-compulsive disorder. In this disorder the
person feels driven to perform certain acts according to rigid rules, in order to prevent or
reducing distress. The person is aware that the behavior is excessive and inappropriate but
can’t stop it. Serotonin has been frequently implicated in obsessive-compulsive disorder. This
is mainly related to the good therapeutic response obtained with serotonergic medications like
SSRIs.
A, B, C, E) (see explanation above)Rate this question:
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- 11.
Receptors located on CNS nerve terminals can be autoreceptors or heteroreceptors. Which of the following descriptions refers to heteroreceptors? (Check all that apply)
- A.
5-HT1A receptors on nerve terminals of most neurons of Raphe Nucleus
- B.
M2 cholinergic receptors on the motor nerve terminals
- C.
Alpha-2 receptors on nerve terminals of most neurons of Locus Ceruleus
- D.
D2 receptors on nerve terminals of nigrostriatal pathway
- E.
GABA A receptors on nerve terminals of cortical pyramidal neurons
- F.
Glutamate receptors on nerve terminals mesolimbic pathway
Correct Answer(s)
E. GABA A receptors on nerve terminals of cortical pyramidal neurons
F. Glutamate receptors on nerve terminals mesolimbic pathwayExplanation
Answer: EF
(Katzung, pp 88, Brunton, pp 148)
By definition heteroreceptors are receptors located on nerve terminals that regulate the
release of a transmitter different from the one that activate them, whereas autoreceptors are
receptors located on nerve terminals that regulate the release of the transmitter which activate
them. Cortical pyramidal neurons are glutamatergic and therefore GABA A receptors located on
nerve terminal of those neurons are heteroreceptors. Neurons of the mesolimbic pathway are
dopaminergic and therefore glutamate receptors located on nerve terminal of those neurons
are heteroreceptors.
A) Most neurons of the Raphe Nucleus are serotonergic an therefore 5-HT1A receptors on
nerve terminals of most neurons
B) Motor neurons are cholinergic and therefore M2 receptors located on nerve terminal of
those neurons are autoreceptors.
C) Most neurons of Locus Ceruleus are noradrenergic and therefore alpha-2 receptors located
on nerve terminal of those neurons are autoreceptors.
D) Neurons of the mesolimbic pathway are dopaminergic and therefore D2 receptors located
on nerve terminal of those neurons are autoreceptors.Rate this question:
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- 12.
A 45-year-old woman, admitted to a psychiatric hospital, has been standing immobile for several hours with one of his arm stretched upwards. The patient was mute, unresponsive and did not appear aware of her surrounding. When placed in another awkward posture the patient maintained that posture for a long time without apparent distress. .Which of the following neurotransmitter has been consistently implicated in the patient’s syndrome?
- A.
Norepinephrine
- B.
Acetylcholine
- C.
Histamine
- D.
Dopamine
- E.
GABA
Correct Answer
D. DopamineExplanation
Answer: D
(Katzung, pp 463, Koda-Kimble, pp 78-3)
The patient is most likely suffering from the catatonic subtype of schizophrenia which is
characterized by motor immobility and abnormal posture maintained for a long time ( the so
called “waxy flexibility”). A number of theories related to major neurotransmitter systems has
been proposed to explain the symptoms of schizophrenia. Of these, the dopamine hypothesis
states that the illness results from an excessive dopaminergic activity in mesolimbic and
mesocortical pathways. The dopamine hypothesis is the most fully developed and is supported
by several lines of evidence, including the fact that most antipsychotic drugs block D2
receptors and there is a very good correlation between clinical potency of these drugs and
their in vitro affinity for these receptors. Other two major hypotheses of schizophrenia are the
serotonin hypothesis (it is known that alteration in serotonergic functioning affects multiple
neurotransmitter systems), and the glutamate hypothesis that proposes a hypofunctional
glutamate system in schizophrenia.
A, B, C, E) (see explanation above)Rate this question:
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- 13.
A 31-year-old woman seeks evaluation in a psychiatric clinic. She reports episodic feeling of sadness since adolescence, but she has noticed a gradual worsening in her mood over the past three weeks. She has depressed mood most of the day, has lost interest in any leisure activity, has difficulty sleeping, poor appetite, low energy, feeling of guilt and recurrent though of death. Which of the following pairs of neurotransmitters are most likely involved in the patient’s disorder?
- A.
Glutamate and serotonin
- B.
Norepinephrine and glutamate
- C.
Glutamate and acetylcholine
- D.
Serotonin and norepinephrine
- E.
Serotonin and acetylcholine
- F.
Acetylcholine and norepinephrine
Correct Answer
D. Serotonin and norepinepHrineExplanation
Answer: D
(Katzung, pp 482, Koda-Kimble, pp 79-4)
The patient has six of the symptoms that are essential features of major depression. Among
the biochemical theories of depression the strongest evidence is for an abnormality in
serotonergic and noradrenergic function. This amine hypothesis of depression is supported by
several lines of evidence including the fact that most antidepressant drugs increase the
availability of serotonin and norepinephrine in the CNS.
A, B, C, E, F) Glutamate and acetylcholine do not seem to be involved in the pathogenesis of
depressionRate this question:
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- 14.
The following table shows the relative activities of five new drugs, which are able to increase the availability of specific CNS neurotransmitters into the synaptic cleft. Examine the table and identify which one of the drugs A, B, C, D, E, is most likely to be effective in the treatment of major obsessive-compulsive disorders. (+ represents the degree of increased availability; - represents negligible effect)
- A.
A
- B.
B
- C.
C
- D.
D
- E.
E
Correct Answer
C. CExplanation
Answer: C
(Katzung, pp 490, Koda-Kimble, pp 76-37)
Drugs that increase the availability of serotonin in the synaptic cleft (like SSRIs and
clomipramine) are the only first line medication treatments for obsessive compulsive disorders.
The pathophysiology of these disorders seems to involve orbitofrontal-limbic-basal ganglia
circuits and, after treatment with SSRIs, functional imaging studies have shown a normalization
of hyperactivity in areas such as the caudate, orbitofrontal lobes and cingulate cortex.
A, B, D, E) (see explanation above)Rate this question:
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- 15.
A 34-year-old man was brought to the emergency room after a serious car accident. He begun to experience sever pain throughout the body. Which of the following triplets of neurotransmitters most likely acted to decrease pain signaling in this patient?
- A.
Norepinephrine, GABA, glutamate
- B.
Glutamate, norepinephrine, opioid peptides
- C.
Histamine, acetylcholine, GABA
- D.
Histamine, acetylcholine, opioid peptides
- E.
Glutamate, GABA, serotonin
- F.
Opioid peptides, norepinephrine, serotonin
Correct Answer
F. Opioid peptides, norepinepHrine, serotoninExplanation
Answer: F
(Katzung, pp 501, Golan, pp 233)
Opioid peptides, serotonin and norepinephrine are the three major neurotransmitters that act in
the CNS to decrease pain signaling and producing analgesia. Endogenous opioids are
released at several CNS sites in response to noxious stimuli, including the spinal cord, the
thalamus and the cortex. Endogenous opioids can also modulate pain transmission indirectly,
by activating the following pathways that descend from the brainstem to the dorsal horn:
a) a noradrenergic pathway from the locus ceruleus. Norepinephrine, released from these
projections in the spinal cord, activates alpha-2 receptors (the primary receptors for
norepinephrine in the CNS) located on nociceptive neurons of the dorsal horn. This activation
causes hyperpolarization of the neuron so inhibiting nociceptive transmission.
b) a serotonergic pathway from the raphe nuclei. Serotonin, released from these projections in
the spinal cord, activates serotonergic receptors located on nociceptive neurons of the dorsal
horn. This activation causes hyperpolarization of the neuron so inhibiting nociceptive
transmission
A, B, C, D, E) (see explanation above)Rate this question:
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- 16.
A 57-year-old woman, suffering from initial insomnia, was prescribed a hypnotic drug that increases the activity of a major neurotransmitter system in the brain. Which of the following neurotransmitter systems is most likely involved in the therapeutic action of that drug?
- A.
Cholinergic
- B.
Noradrenergic
- C.
Glutamatergic
- D.
GABAergic
- E.
Dopaminergic
- F.
Endorphinergic
Correct Answer
D. GABAergicExplanation
Answer: D
(Katzung, pp 357, Brunton, pp 405)
Most drugs used to relieve insomnia (i.e. benzodiazepines, zolpidem) are GABAergic drugs,
that is they increase the activity of GABA, the most abundant inhibitory neurotransmitter in the
brain.
A, B, C, E, F) Drugs acting on these neurotransmitter systems are not currently used to treat
insomnia.Rate this question:
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- 17.
A 76-year-old man, suffering from Alzheimer’s disease, was prescribed a drug that increases the central levels of a neurotransmitter thought to play an important role in cognitive functions. Which of the following neurotransmitters was most likely increased by that drug?
- A.
Acetylcholine
- B.
Norepinephrine
- C.
Histamine
- D.
GABA
- E.
Dopamine
Correct Answer
A. AcetylcholineExplanation
Answer: A
(Katzung, pp 1010 , Brunton, pp 539)
The main class of drugs currently approved for the treatment of Alzheimer’s disease are
cholinesterase inhibitors, which increase the central levels of acetylcholine. Patients with
Alzheimer’s disease have a significant loss of cholinergic neurons especially in the temporal
lobe and entorhinal cortex, two areas responsible for maintaining memory and cognition.
B, C, D, E) (see explanation above)Rate this question:
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- 18.
A 18-year-old boy was brought to the emergency room by a friend after being found acting crazy in a discotheque. The man admitted he had smoked an “angel dust”, the street name for phencyclidine. Which of the following neurotransmitters seems mainly involved in the mechanism of action of that drug?
- A.
Acetylcholine
- B.
Histamine
- C.
Glycine
- D.
GABA
- E.
Glutamate
Correct Answer
E. GlutamateExplanation
Answer: E
(Katzung, pp 524, Brunton, pp 625)
Phencyclidine is a hallucinogenic drug that binds with high affinity and blocks the N-methyl-Daspartate
(NMDA) subtype of glutamate receptor in the brain. A closely related drug, ketamine,
seems to act in a similar way ,is used as a general anesthetic agent but is sometimes abused
(with the street name of special K).
A, B, C, D) (see explanation above)Rate this question:
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- 19.
A 28-year-old man with a long history of poly-drug abuse states he feels an intense euphoric sensation every time he self administered any illicit drug. Which of the following neurotransmitters, released in the nucleus accumbens, is thought to mediate the rewarding effect of most abused drugs?
- A.
Acetylcholine
- B.
Norepinephrine
- C.
Histamine
- D.
GABA
- E.
Dopamine
Correct Answer
E. DopamineExplanation
Answer: E
(Katzung, pp 518, Graham, pp 65)
Acute rewarding effects of most abused drug are thought to be mediated by and increased in
synaptic levels of dopamine in nucleus accumbens, a nucleus that seems to comprise a major
portion of the brain reward circuitry. Because of this, dopamine is thought to play an important
role in the development of drug dependence.
A, B, C, D) (see explanation above)Rate this question:
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- 20.
A 79-year-old woman complained of sharp headache in the temporal area. Fifteen minutes later she lost consciousness and was brought to the Emergency Room. A CT scan showed a diffuse brain hemorrhage and the diagnosis of left middle cerebral artery stoke was made. Which of the following neurotransmitters has been implicated as a cause of cell death following stroke?
- A.
Acetylcholine
- B.
Norepinephrine
- C.
GABA
- D.
Serotonin
- E.
Glutamate
Correct Answer
E. GlutamateExplanation
Answer: E
(Katzung, pp 347, Brunton, pp 332)
Although glutamate is essential for brain function, too much glutamate can be toxic to neurons.
When blood flow to the brain tissue is impaired, mechanism of normal glutamate reuptake
stops and glutamate accumulates into the synaptic cleft. This high concentration of glutamate
can activate a large amount of glutamate ionotropic receptors, so triggering a huge influx of
Ca++ into postsynaptic cells. This intracellular high Ca++ level can cause neuronal death. This
property of glutamate is called excitotoxicity and can play an important role in a number of
brain disorders including stroke and epilepsy.
A, B, C, D) These neurotransmitters do not cause excitotoxicity.Rate this question:
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.JPG "The following table shows the relative activities of five new drugs, which are able to
increase the availability of specific CNS neurotransmitters into the synaptic cleft.
Examine the table and identify which one of the drugs A, B, C, D, E, is most likely to be
effective in the treatment of major obsessive-compulsive disorders. (+ represents the
degree of increased availability; - represents negligible effect)")
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