Psychopharm3e Ch06 Test Bank

Test Bank
to accompany
Psychopharmacology, Third Edition
Meyer • Quenzer
Chapter 6: Serotonin
Multiple Choice
1. Another name for serotonin is

a. 5-hydroxytryptophan.
b. tryptophan.
c. 5-hydroxytryptamine.
d. tryptamine.
Answer: c
Textbook Reference: Introduction
2. A specific marker for serotonin cells is

a. tyrosine hydroxylase.
b. tryptophan hydroxylase.
c. AADC.
d. MAO.
Answer: b
Textbook Reference: Serotonin Synthesis, Release, and Inactivation
3. What type of meal is most likely to increase brain levels of serotonin in animals?
a. High carbohydrate, high protein
b. High carbohydrate, low protein
c. Low carbohydrate, low protein
d. Low carbohydrate, high protein
Answer: b
4. Why might increasing levels of tryptophan in the blood not increase brain serotonin
levels?
a. It doesn’t matter how much tryptophan is present, serotonin is made at a constant rate
from brain stores of tryptophan.
b. Tryptophan cannot cross the blood–brain barrier under any circumstances.
c. Tryptophan competes with other amino acids for transport across the blood–brain
barrier.
d. Insulin is required for transport of tryptophan across the blood–brain barrier.
Answer: c
5. In order to study the effects of serotonin depletion in rodent studies,

a. tryptophan hydroxylase is inhibited by injection of PCPA.
b. tryptophan hydroxylase is stimulated by injection of PCPA.
c. animals are fed a high carbohydrate, low protein diet.
d. insulin is injected to alter the ratio of amino acids in the blood.
Answer: a
6. Researchers study the effects of serotonin depletion in human subjects by

a. using the synthesis blocking drug PCPA.
b. administering a special milkshake that is rich in tryptophan hydroxylase.
c. injecting subjects with insulin to alter the ratio of amino acids in the blood.
d. administering a cocktail of amino acids that compete with tryptophan for entry into the
brain.
Answer: d
7. One potential consequence of administration of an amino acid cocktail to human

subjects is that
a. depressed subjects may experience a total remission of depressive symptoms if given a
tryptophan-free cocktail.
b. serotonin syndrome can result.
c. previously healthy subjects can develop depression and anxiety if given a tryptophan-
containing cocktail.
d. previously depressed but currently recovered patients maintained on a 5-HT-based
antidepressant developed symptoms of depression if given a tryptophan-free cocktail.
Answer: d
8. All of the following can increase the presence of serotonin in the synaptic cleft except
a. DOI.
b. MDMA.
c. fenfluramine.
d. fluoxetine.
Answer: a
9. Autoreceptors on serotonin terminals are of the _______ subtype, while

somatodendritic autoreceptors are of the _______ subtype.
a. 5-HT1A; 5-HT3
b. 5-HT1A; 5-HT1B or 5-HT1D
c. 5-HT1B or 5-HT1D; 5-HT1A
d. 5-HT3; 5-HT1A
Answer: c
10. The deactivation and metabolism of serotonin

a. involves removal from the cleft by COMT.
b. can be increased by SSRIs like Prozac.
c. is selectively affected by the neurotoxin MDMA.
d. yields the metabolite 5-HIAA.
Answer: d
11. The principal acute action of MDMA is to

a. prevent reuptake of serotonin.
b. inhibit synthesis of serotonin.
c. enhance tryptophan transport.
d. enhance serotonin release.
Answer: d
12. MDMA was originally synthesized by the Merck pharmaceutical company as part of
a project to find new substances that would
a. reduce appetite.
b. stop bleeding.
c. reduce anxiety or nervousness.
d. increase energy.
Answer: b
13. Which statement about MDMA is false?

a. It produces an altered state of consciousness.
b. It has been proposed as an adjunct to psychotherapy because it can enhance empathy.
c. It has definitively been shown to produce degeneration of nerve fibers in all human
users.
d. It is considered a Schedule I substance according to the DEA.
Answer: c
14. MDMA has recently been shown to improve the clinical response in patients
undergoing treatment for
a. PTSD.
b. drug addiction.
c. anexoria.
d. depression.
Answer: a
15. Knockout mice lacking the serotonin transporter SERT exhibit all of the following
except
a. hypoactivity.
b. a decrease in aggressiveness.
c. enhanced maternal behavior.
d. anxiety-like behavior.
Answer: c
16. The activity of serotonergic neurons in humans can be determined indirectly by

measuring
a. levels of 5-HIAA in cerebrospinal fluid.
b. levels of 5-HIAA in blood.
c. levels of 5-HT in cerebrospinal fluid.
d. activation of SERT.
Answer: a
17. Most of the cell bodies that produce serotonin in the CNS are found in the
a. cerebellum.
b. raphe nuclei.
c. thalamus.
d. limbic system.
Answer: b
Textbook Reference: Organization and Function of the Serotonergic System
18. The fibers of serotonergic neurons are found

a. mainly in the cerebellum and spinal cord.
b. mainly in the midbrain, hypothalamus, and thalamus.
c. mainly in the midbrain, pons, and medulla.
d. in virtually all forebrain areas.
Answer: d
19. Serotonergic neurons in the cat dorsal raphe nucleus stop firing during which
behavioral state?
a. REM sleep
b. Active waking
c. Slow-wave sleep
d. Quiet waking
Answer: a
20. Pharmacologists have identified at least _______ different receptor subtypes for
serotonin, most of which are _______.
a. 14; ionotropic
b. 7; ionotropic
c. 7; metabotropic
d. 14; metabotropic
Answer: d
21. All serotonin receptors are _______ except for the _______ receptor, which is
_______.
a. metabotropic; 5-HT5B; ionotropic
b. metabotropic; 5-HT3; ionotropic
c. ionotropic; 5-HT2C; metabotropic
d. ionotropic; 5-HT1C; metabotropic
Answer: b
22. Which statement about 5-HT1A receptors is false?

a. They serve as somatodendritic autoreceptors in the dorsal raphe nuclei.
b. They are located postsynaptically in the forebrain.
c. They serve as autoreceptors on serotonergic axon terminals in the forebrain.
d. They are concentrated in the hippocampus, septal area, and parts of the amygdala.
Answer: c
23. Activation of 5HT1A serotonin receptors can result in all of the following except a(n)
a. increase in Na+ conductance across the cell membrane.
b. reduction in cAMP synthesis.
c. increase in K+ conductance.
d. decrease in firing of the serotonergic neuron.
Answer: a
24. Activation of 5HT1A serotonin receptors causes the neuronal membrane to be

_______ because _______ channels are opened.
a. hyperpolarized; K+
b. depolarized; K+
c. hyperpolarized; Ca2+
d. depolarized; Na+
Answer: a
25. Information regarding the effects of endogenous 5-HT on 5-HT1A receptors can be
determined by administration of an antagonist such as
a. busprione.
b. 8-OH-DPAT.
c. WAY 100635.
d. ipsapirone.
Answer: c
26. Like α1-adrenergic receptors, _______ receptors activate the phosphoinositide
second-messenger system and thus increase intracellular _______ levels.
a. 5-HT2A; Ca2+
b. 5-HT1A; K+
c. 5-HT2A; cAMP
d. 5-HT2A; Na+
Answer: a
27. Which statement regarding the serotonin receptor family is true?

a. 5-HT1A receptors are located primarily in the cerebral cortex.
b. 5-HT2A receptors cause inhibition by decreasing adenyl cyclase and increasing
potassium efflux.
c. There is a family of five different 5-HT1 receptors.
d. LSD and similar hallucinogens are most likely agonists at the 5-HT1A receptor.
Answer: c
28. Drugs that act as agonists at 5-HT2A receptors produce a characteristic “head-twitch”
response in rodents and _______ in humans.
a. unwanted motor responses
b. hallucinations
c. Parkinsonian symptoms
d. antischizophrenic effects
Answer: b
29. Later generation drugs used to treat schizophrenia, such as clozapine and risperidone,
block/activate _______ receptors and produce _______ motor side effects.
a. D2; severe
b. 5-HT2A; fewer
c. 5-HT2A; severe
d. both D2 and 5-HT2A; severe
Answer: b
30. Anti-migraine drugs known as triptans act as _______ and cause _______ of blood
vessels.
a. 5HT1A agonists; constriction
b. 5-HT3 antagonists; dilation
c. 5-HT1B/1D antagonists; constriction
d. 5-HT1B/1D agonists; constriction
Answer: d
31. Which statement regarding 5-HT3 receptors is false?

a. Some of them are located on peripheral terminals of the vagus nerve.
b. Activation of these receptors inhibits the vomiting center in the brainstem.
c. Drugs that block this receptor subtype are used to treat nausea in cancer chemotherapy
patients.
d. Ondansetron, granisetron, and palonosetron are all 5-HT3 receptor antagonists.
Answer: b
32. 5,7-Dihydroxytryptamine (5,7-DHT)

a. is a metabolite of serotonin.
b. destroys the cell bodies of the serotonergic neurons.
c. inhibits serotonin synthesis.
d. must be administered directly into the brain.
Answer: d
33. Which method(s) can be used to produce mice that lack brain serotonin throughout
life, beginning with embryonic development?
a. Administering the tryptophan hydroxylase inhibitor PCPA
b. Knocking out the gene for tryptophan hydroxylase 2
c. Preventing the normal differentiation of cells that are destined to become serotonergic
neurons
d. Both b and c
Answer: d
34. In mice with a knockout of the tryptophan hydroxylase 2 gene,

a. no serotonin can be synthesized in any part of the animal's body.
b. no pharmacological treatment has been found that is able to restore serotonin, even
temporarily.
c. the circuitry of the serotonergic system (fiber innervation) is normal, despite the lack of
serotonin.
d. impulsive aggression is increased compared to wild-type mice.
Answer: d
35. Which type of aggression is not observed in animals?

a. Premeditated aggression
b. Predatory aggression
d. Maternal aggression
d. Irritable aggression
Answer: a
36. One brain region implicated in the neural circuitry of aggression in rodents but not in
humans is the
a. amygdala.
b. cingulate cortex.
c. BNST.
d. hypothalamus.
Answer: c
37. Evidence supporting a link between low levels of 5-HT and/or receptor activation and
increased aggression, or high levels of 5-HT and/or receptor activation and decreased
aggression, comes from all of the following studies except for those
a. measuring 5-HT release during play of violent video games.
b. correlating 5-HIAA concentration in the cerebrospinal fluid and measures of
aggressive behavior.
c. using SSRIs to increase extracellular 5-HT levels.
d. examining inhibition of tryptophan hydroxylase.
Answer: a
38. Mice genetically engineered to lack central serotonin

a. do not survive to birth.
b. have difficulty with thermoregulation.
c. demonstrate little to no aggressive behavior.
d. breathe at a faster rate than wild-type mice.
Answer: b
39. Evidence that serotonergic abnormalities may be involved in sudden infant death
syndrome (SIDS) comes from studies showing that
a. the incidence of SIDS decreases if infants are given SSRIs.
b. response to a CO2 challenge in mutant mice lacking central serotonin can be improved
by treatment with DOI.
c. apnea in mutant mice lacking central serotonin can be reversed with SSRIs.
d. infants who died of SIDS had a reduced number of 5-HT2A receptors in their brain.
Answer: b
40. Administration of _______ is not likely to lead to a decrease in food intake and thus
weight loss.
a. 5-HT1B agonists
b. 5-HT2C agonists
c. 5-HT1A agonists
d. 5-HT6 antagonists
Answer: c
41. Which statement regarding serotonin and anxiety is false?

a. Buspirone is an effective antianxiety medication and a partial agonist at 5-HT1A
receptors.
b. Knockout mice lacking 5-HT1A receptors show increased anxiety on the elevated zero
maze.
c. Knockout mice lacking 5-HT2A receptors show decreased anxiety-like behaviors.
d. The 5-HT2A/2C receptor agonist mCPP is an effective antianxiety medication.
Answer: d
42. Studies using animal models have shown that serotonin is involved in _______ pain.
a. cancer-related
b. neuropathic
c. hypoalgesia
d. electric shock-induced
Answer: b
43. Administration of a 5-HT4 receptor partial agonist

a. impairs memory consolidation in a 1-trial fear conditioning task.
b. improves cognitive function in patients with Alzheimer’s disease.
c. enhances learning and memory in various learning tasks in rodents and monkeys.
d. affects cognitive function by inhibiting cholinergic transmission in the neocortex and
hippocampus.
Answer: c
44. The 5-HT6 antagonist ________ is being tested as a potential therapeutic agent to
improve cognitive function in patients with Alzheimer’s disease.
a. idalopirdine
b. donepezil
c. vilazodone
d. lorcaserin
Answer: a
45. In the gut, serotonin is synthesized by

a. some neurons within the enteric nervous system.
b. enterochromaffin cells.
c. goblet cells.
d. Both a and b
Answer: d
46. Serotonin release in the gut is stimulate by

a. taking an SSRI.
b. fasting.
c. entry of food into the gut.
d. Both a and c
Answer: c
47. One of the current treatments for irritable bowel syndrome (IBS) is alosetron, which
acts as a
a. 5-HT3 receptor antagonist.
b. 5-HT6 recept or agonist.
c. 5-HT4 receptor antagonist.
d. 5-HT2 receptor agonist.
Answer: a
Short Answer/Essay
48. Describe the synthesis of serotonin and explain why serotonin levels in the brain can
be increased by consumption of a high-carbohydrate, low-protein meal.
Answer: Serotonin is synthesized from tryptophan in two steps: tryptophan to 5-
hydroxytryptophan (5-HTP), catalyzed by tryptophan hydroxylase; and 5-HTP to
serotonin, catalyzed by aromatic amino acid decarboxylase. Serotonin levels in the brain
can be increased by consuming a high-carbohydrate, low-protein meal because
tryptophan competes with other large neutral amino acids for transport into the brain
across the blood–brain barrier. Consumption of a high-carbohydrate, low-protein meal
triggers insulin release, increases the ratio of plasma tryptophan to its competing amino
acids, and thus increasing tryptophan entry into the brain.
49. Explain the primary mechanism responsible for rapid termination of serotonergic
transmission, and name an important class of drugs that acts on that mechanism.
Answer: Serotonergic transmission is rapidly terminated by reuptake by the 5-HT
transporter. A major class of drugs acting on this mechanism are the selective serotonin
reuptake inhibitors (SSRIs).
50. Describe the primary acute mechanism of action of MDMA. What experimental
evidence would you cite to convince someone not to take repeated high doses of MDMA
(ecstasy)?
Answer: MDMA acutely releases serotonin from serotonergic neurons. Animal studies
have shown that high doses of MDMA cause long-term reductions in brain serotonin
levels and in serotonergic fiber staining. Long-term ecstasy exposure in humans has also
been found to produce abnormalities in the serotonergic system and cognitive deficits.
51. Name the major serotonin cell clusters in the brain stem and describe their projection
pathways.
Answer: The major serotonin cell clusters in the brain stem are the raphe nuclei,
especially the dorsal and median raphe. These cells project to virtually all forebrain areas,
including the neocortex, striatum, nucleus accumbens, thalamus, hypothalamus, and
limbic system structures (hippocampus, amygdala, and septal area).
52. Describe the changes in dorsal raphe cell firing rate during different behavioral states
in cats.
Answer: Firing is steady at a rate of 2 spikes per second during quiet waking. Firing is
slightly increased during behavioral activity, greatly reduced during slow-wave sleep, and
abolished during REM sleep.
53. Identify the two ways by which 5-HT1A receptors exert their postsynaptic effects. List
two kinds of evidence supporting a role for 5-HT1A receptors in regulating anxiety.
Answer: 5-HT1A receptors inhibit adenylyl cyclase/reduce the rate of cAMP synthesis,
and increase the opening of K+ channels to cause membrane hyperpolarization. Evidence
for regulating anxiety: The 5-HT1A partial agonist buspirone is used as an antianxiety
medication, and 5-HT1A receptor knockout mice exhibit increased anxiety-like behavior
in several standard behavioral tests.
54. How do 5-HT2A receptors exert their postsynaptic effects? Give an example of a 5-
HT2A receptor agonist and a 5-HT2A receptor antagonist.
Answer: 5-HT2A receptors activate the phosphoinositide second messenger system. DOI
is an agonist; ketanserin and ritanserin are antagonists.
55. Explain what makes 5-HT3 receptors different from other serotonin receptors.
Identify one important therapeutic use of 5-HT3 receptor antagonists.
Answer: Unlike other serotonin receptors, 5-HT3 receptors are excitatory ionotropic
receptors. 5-HT3 receptor antagonists are used therapeutically to counteract nausea and
vomiting associated with cancer chemotherapy.
56. Describe the evidence linking serotonin and aggression in both humans and animal
models. Give examples involving specific serotonin receptor subtypes.
Answer: Reduced cerebrospinal fluid concentrations of 5-HIAA have been linked to
increased aggressiveness in patients with borderline personality disorder or more
generally in people who exhibit antisocial behavior. In animal studies, aggressive
behavior was decreased by administration of an SSRI, whereas aggressive behavior was
increased by administration of a serotonin neurotoxin or a tryptophan hydroxylase
inhibitor. Administration to rodents of either a 5-HT1A or a 5-HT1B receptor agonist
reduces aggressive behavior, possibly due to the autoreceptor activity of these drugs.
57. Explain how techniques of genetic engineering have contributed to our understanding
of the behavioral and physiological functions of the serotonergic system.
Answer: Knockout mice have been generated in which key serotonergic genes such as the
tryptophan hydroxylase gene, the serotonin transporter gene, or the genes for particular
serotonergic receptors have been inactivated. By investigating the behavioral and/or
physiological phenotypes produced by loss of a specific gene, researchers can infer the
functional role(s) of the missing gene. In the case of the tryptophan hydroxylase2 (TPH2)
gene, the effects of the knockout are due to a global loss of serotonin synthesis
throughout the nervous system. In the case of the serotonin transporter gene, the effects
of the knockout are due to a global increase in extracellular serotonin levels because of
the loss of reuptake. In the case of specific receptor knockouts, the phenotype reflects the
functional role of that serotonin receptor in behavioral and physiological regulation.
58. Imagine you are in charge of research and development of a pain medication program
at a major pharmaceutical company. Assuming that you are targeting the serotonergic
system in your drug development program, what pain model should you focus on? What
kinds of changes in pain sensitivity have been associated with this pain model? List two
different serotonergic receptors for which agonist drugs have been successful in
alleviating pain in animal research.
Answer: The pain model to focus on is neuropathic pain, which has been associated with
hyperalgesia and allodynia. Agonists at the 5-HT1A, 5-HT1B, 5-HT2C, and 5-H7 have been
shown to reduce models of neuropathic pain in animal studies.
59. Where does gut serotonin come from, what triggers its release, and what is its
function?
Answer: Gut serotonin comes from neurons of the enteric nervous system and from
enterochromaffin cells in the walls of the gut. Release of gut serotonin is triggered by
ingestion of food. Serotonin functions to promote gut peristalsis and secretory activity.

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1. Another name for serotonin is

2. A specific marker for serotonin cells is

5. In order to study the effects of serotonin depletion in rodent studies,

6. Researchers study the effects of serotonin depletion in human subjects by

7. One potential consequence of administration of an amino acid cocktail to human

9. Autoreceptors on serotonin terminals are of the _______ subtype, while

10. The deactivation and metabolism of serotonin

11. The principal acute action of MDMA is to

13. Which statement about MDMA is false?

16. The activity of serotonergic neurons in humans can be determined indirectly by

18. The fibers of serotonergic neurons are found

22. Which statement about 5-HT1A receptors is false?

24. Activation of 5HT1A serotonin receptors causes the neuronal membrane to be

27. Which statement regarding the serotonin receptor family is true?

31. Which statement regarding 5-HT3 receptors is false?

32. 5,7-Dihydroxytryptamine (5,7-DHT)

34. In mice with a knockout of the tryptophan hydroxylase 2 gene,

35. Which type of aggression is not observed in animals?

38. Mice genetically engineered to lack central serotonin

41. Which statement regarding serotonin and anxiety is false?

43. Administration of a 5-HT4 receptor partial agonist

45. In the gut, serotonin is synthesized by

46. Serotonin release in the gut is stimulate by

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