Deck 6: Serotonin
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Deck 6: Serotonin
1
A specific marker for serotonin cells is
A) tyrosine hydroxylase (TH).
B) tryptophan hydroxylase (TPH).
C) AADC.
D) MAO.
A) tyrosine hydroxylase (TH).
B) tryptophan hydroxylase (TPH).
C) AADC.
D) MAO.
B
2
What type of meal is most likely to increase brain levels of tryptophan in animals?
A) High carbohydrate, high protein
B) High carbohydrate, low protein
C) Low carbohydrate, low protein
D) Low carbohydrate, high protein
A) High carbohydrate, high protein
B) High carbohydrate, low protein
C) Low carbohydrate, low protein
D) Low carbohydrate, high protein
B
3
Most of the tryptophan obtained through diet is converted to _______, through the actions of _______.
A) glucose; MAO and IDO
B) kynurenine; IDO or TDO
C) glucose; MAO or COMT
D) kynurenine; COMT or TDO
A) glucose; MAO and IDO
B) kynurenine; IDO or TDO
C) glucose; MAO or COMT
D) kynurenine; COMT or TDO
B
4
Why might increasing levels of tryptophan in the bloodstream not increase brain serotonin levels as would be expected?
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.
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.
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5
In order to study the effects of serotonin depletion in rodent studies,
A) tryptophan hydroxylase is inhibited by injection of para-chlorophenylalanine (PCPA).
B) tryptophan hydroxylase is stimulated by injection of para-chlorophenylalanine (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.
A) tryptophan hydroxylase is inhibited by injection of para-chlorophenylalanine (PCPA).
B) tryptophan hydroxylase is stimulated by injection of para-chlorophenylalanine (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.
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6
Researchers study the effects of serotonin depletion in human subjects by inducing _______, which is accomplished by _______.
A) LNAA; using the synthesis-blocking drug PCPA
B) ATD; administering a special milkshake that is rich in tryptophan hydroxylase
C) LNAA; injecting subjects with insulin to alter the ratio of amino acids in the blood
D) ATD; administering a "cocktail" of amino acids that compete with tryptophan for entry into the brain
A) LNAA; using the synthesis-blocking drug PCPA
B) ATD; administering a special milkshake that is rich in tryptophan hydroxylase
C) LNAA; injecting subjects with insulin to alter the ratio of amino acids in the blood
D) ATD; administering a "cocktail" of amino acids that compete with tryptophan for entry into the brain
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7
One potential consequence of acute tryptophan depletion, (ATD) therapy is that
A) it can impair working memory.
B) it can lead to serotonin syndrome.
C) patients with clinical depression taking an antidepressants that act on the adrenergic system may experience a relapse in their symptoms.
D) patients with clinical depression taking an antidepressants that act on the serotonergic system may experience a relapse in their symptoms.
A) it can impair working memory.
B) it can lead to serotonin syndrome.
C) patients with clinical depression taking an antidepressants that act on the adrenergic system may experience a relapse in their symptoms.
D) patients with clinical depression taking an antidepressants that act on the serotonergic system may experience a relapse in their symptoms.
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8
All of the following drugs result in an increase in serotonin levels except
A) DOI.
B) MDMA.
C) fenfluramine.
D) fluoxetine.
A) DOI.
B) MDMA.
C) fenfluramine.
D) fluoxetine.
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9
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) Creating knockout mice that lack 5-HT
C) Preventing the normal differentiation of cells that are destined to become serotonergic neurons
D) Both b and c
A) Administering the tryptophan hydroxylase inhibitor PCPA
B) Creating knockout mice that lack 5-HT
C) Preventing the normal differentiation of cells that are destined to become serotonergic neurons
D) Both b and c
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10
Findings based on ATD and tyrosine hydroxylase inhibitor depletion studies support the theory that the underlying causes of differing symptoms among people with mood or anxiety disorders may be related to abnormalities in
A) signaling among peptide hormones.
B) the parasympathetic versus the sympathetic nervous systems.
C) the limbic system.
D) the serotonergic versus the catecholaminergic systems.
A) signaling among peptide hormones.
B) the parasympathetic versus the sympathetic nervous systems.
C) the limbic system.
D) the serotonergic versus the catecholaminergic systems.
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11
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
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
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12
The deactivation and metabolism of serotonin
A) involves reuptake by COMT.
B) can be increased by SSRIs like Prozac.
C) is selectively affected by the neurotoxin MDMA.
D) yields the metabolite 5-HIAA.
A) involves reuptake by COMT.
B) can be increased by SSRIs like Prozac.
C) is selectively affected by the neurotoxin MDMA.
D) yields the metabolite 5-HIAA.
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13
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.
A) hypoactivity.
B) a decrease in aggressiveness.
C) enhanced maternal behavior.
D) anxiety-like behavior.
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14
If a researcher was exploring a possible link between the activity of serotonergic neurons and behavioral traits in a group of people with personality disorders, she might measure in _______ in these subjects.
A) levels of 5-HIAA in the CSF
B) levels of 5-HIAA in the bloodstream
C) levels of 5-HT in the CSF
D) activity of SERT
A) levels of 5-HIAA in the CSF
B) levels of 5-HIAA in the bloodstream
C) levels of 5-HT in the CSF
D) activity of SERT
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15
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.
A) reduce appetite.
B) stop bleeding.
C) reduce anxiety or nervousness.
D) increase energy.
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16
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.
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.
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17
MDMA has been shown to improve the clinical response in patients undergoing treatment for
A) PTSD.
B) drug addiction.
C) anorexia.
D) depression.
A) PTSD.
B) drug addiction.
C) anorexia.
D) depression.
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18
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.
A) prevent reuptake of serotonin.
B) inhibit synthesis of serotonin.
C) enhance tryptophan transport.
D) enhance serotonin release.
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19
_______ syndrome is caused by neuroendocrine tumors that release an overabundance of _______ into the bloodstream.
A) Carcinoid; 5-HT
B) Serotonin; α-MSH
C) Carcinoid; Ca2+
D) Serotonin; K+
A) Carcinoid; 5-HT
B) Serotonin; α-MSH
C) Carcinoid; Ca2+
D) Serotonin; K+
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20
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.
A) cerebellum.
B) raphe nuclei.
C) thalamus.
D) limbic system.
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21
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.
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.
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22
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
A) REM sleep
B) Active waking
C) Slow-wave sleep
D) Quiet waking
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23
Experiments with mice show that slow, tonic firing of DRN neurons promotes _______, while burst firing of these neurons promotes _______.
A) hyperactivity; sedation
B) aggression; fear
C) sleep; wakefulness
D) anorexia; feeding behavior
A) hyperactivity; sedation
B) aggression; fear
C) sleep; wakefulness
D) anorexia; feeding behavior
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24
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
A) 14; ionotropic
B) 7; ionotropic
C) 7; metabotropic
D) 14; metabotropic
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25
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
A) metabotropic; 5-HT5B; ionotropic
B) metabotropic; 5-HT3; ionotropic
C) ionotropic; 5-HT2C; metabotropic
D) ionotropic; 5-HT1C; metabotropic
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26
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.
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.
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27
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.
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.
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28
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+
A) hyperpolarized; K+
B) depolarized; K+
C) hyperpolarized; Ca2+
D) depolarized; Na+
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29
Information regarding the effects of endogenous 5-HT on 5-HT1A receptors can be determined by administration of an antagonist such as
A) buspirone.
B) 8-OH-DPAT.
C) WAY-100635.
D) ipsapirone.
A) buspirone.
B) 8-OH-DPAT.
C) WAY-100635.
D) ipsapirone.
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30
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+
A) 5-HT2A; Ca2+
B) 5-HT1A; K+
C) 5-HT2A; cAMP
D) 5-HT2A; Na+
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31
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.
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.
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32
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
A) unwanted motor responses
B) hallucinations
C) Parkinsonian symptoms
D) antischizophrenic effects
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33
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
A) 5HT1A agonists; constriction
B) 5-HT3 antagonists; dilation
C) 5-HT1B/1D antagonists; constriction
D) 5-HT1B/1D agonists; constriction
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34
Traditional medications used to treat migraines work by constricting blood vessels. In contrast the 5-HT1F agonist lasmiditan acts by
A) decreasing activity within the pain pathway.
B) increasing release of endorphins.
C) reducing blood pressure.
D) enhancing vagal transmission of serotonin to the brain.
A) decreasing activity within the pain pathway.
B) increasing release of endorphins.
C) reducing blood pressure.
D) enhancing vagal transmission of serotonin to the brain.
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35
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.
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.
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36
Mice genetically engineered to lack central serotonin
A) do not survive to birth.
B) demonstrate little to no aggressive behavior.
C) have difficulty with thermoregulation.
D) breathe at a faster rate than wild-type mice.
A) do not survive to birth.
B) demonstrate little to no aggressive behavior.
C) have difficulty with thermoregulation.
D) breathe at a faster rate than wild-type mice.
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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 studies
A) measuring 5-HT release during play of violent video games.
B) correlating 5-HIAA concentration in the CSF and brain to measures of aggressive behavior.
C) using PCPA to increase extracellular 5-HT levels.
D) determining the ratio TPH to 5H-T in the bloodstream.
A) measuring 5-HT release during play of violent video games.
B) correlating 5-HIAA concentration in the CSF and brain to measures of aggressive behavior.
C) using PCPA to increase extracellular 5-HT levels.
D) determining the ratio TPH to 5H-T in the bloodstream.
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38
A mouse is tested in the elevated plus-maze and shows extreme anxiety compared to other mice. From this observation you surmise that this mouse likely
A) is a 5-HT4-knockout mouse.
B) has been treated with a selective 5-HT2C agonist.
C) is a 5-HT1A-knockout mouse.
D) has been treated with a 5-HT1A receptor agonist.
A) is a 5-HT4-knockout mouse.
B) has been treated with a selective 5-HT2C agonist.
C) is a 5-HT1A-knockout mouse.
D) has been treated with a 5-HT1A receptor agonist.
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39
Similar brain areas have been shown to be involved in fear/anxiety and aggression. Thus, before reacting to a threat a person evaluates present context and past experience, which dictates whether the person's response to the threat is _______ or _______.
A) defensive; aggressive
B) delayed; immediate
C) unpredictable; predictable
D) overreactive; underreactive
A) defensive; aggressive
B) delayed; immediate
C) unpredictable; predictable
D) overreactive; underreactive
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40
Which scenario provides evidence supporting the serotonin deficiency hypothesis?
A) Mice administered PCPA show a decrease in aggressive behavior.
B) A person with impulsive aggression is prescribed a relatively high dose of an SSRI, which reduces this behavior.
C) Mice are fed a diet high in tryptophan and show an increase in aggressive behavior.
D) A person with impulsive aggression is treated with ATD, which reduces this behavior.
A) Mice administered PCPA show a decrease in aggressive behavior.
B) A person with impulsive aggression is prescribed a relatively high dose of an SSRI, which reduces this behavior.
C) Mice are fed a diet high in tryptophan and show an increase in aggressive behavior.
D) A person with impulsive aggression is treated with ATD, which reduces this behavior.
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41
Administration of _______ leads to a decrease in food intake, weight loss and other benefits for people that are overweight, such as lowering diabetes risk.
A) 5-HT4 agonists
B) 5-HT2C agonists
C) 5-HT3 antagonists
D) 5-HT6 antagonists
A) 5-HT4 agonists
B) 5-HT2C agonists
C) 5-HT3 antagonists
D) 5-HT6 antagonists
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42
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
A) some neurons within the enteric nervous system.
B) enterochromaffin cells.
C) goblet cells.
D) Both a and b
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43
Serotonin release in the gut is stimulated by
A) triptan drugs.
B) fasting.
C) entry of food into the gut.
D) anxiolytic drugs.
A) triptan drugs.
B) fasting.
C) entry of food into the gut.
D) anxiolytic drugs.
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44
One of the current treatments for irritable bowel syndrome IBS-D is alosetron, which acts as a
A) 5-HT3 antagonist.
B) 5-HT6 agonist.
C) 5-HT4 antagonist.
D) 5-HT2 agonist.
A) 5-HT3 antagonist.
B) 5-HT6 agonist.
C) 5-HT4 antagonist.
D) 5-HT2 agonist.
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45
The hypothalamic circuit that includes neuropeptide-releasing neurons within the arcuate nucleus that project to melanocortin receptor neurons in the paraventricular nucleus is involved in the sensation of
A) sedation.
B) fear.
C) aggression.
D) hunger.
A) sedation.
B) fear.
C) aggression.
D) hunger.
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46
The enteric nervous system plays the most important role in mediating serotonergic effects on gut function. However, researchers originally thought that enterochromaffin cells played the most important role because
A) experiments with knockout mice suggested greater involvement of enterochromaffin cells.
B) of the sheer number of enterochromaffin cells in the gut.
C) of the high density of 5-HT in enterochromaffin cells.
D) enterochromaffin 5-HT is released directly into the bloodstream.
A) experiments with knockout mice suggested greater involvement of enterochromaffin cells.
B) of the sheer number of enterochromaffin cells in the gut.
C) of the high density of 5-HT in enterochromaffin cells.
D) enterochromaffin 5-HT is released directly into the bloodstream.
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47
Signaling between the gut 5-HT and the brain is supported by several studies, one of which showed that firing rate of vagal afferents from the gut was increased by administration
A) of a catecholamine reuptake inhibitor, but not by an SSRI.
B) of an SSRI, but not by a catecholamine reuptake inhibitor.
C) of PCPA, but not by a catecholamine reuptake inhibitor.
D) of MDMA, but not by a catecholamine reuptake inhibitor.
A) of a catecholamine reuptake inhibitor, but not by an SSRI.
B) of an SSRI, but not by a catecholamine reuptake inhibitor.
C) of PCPA, but not by a catecholamine reuptake inhibitor.
D) of MDMA, but not by a catecholamine reuptake inhibitor.
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48
Which type of aggression has not been observed in animals?
A) Premeditated aggression
B) Predatory aggression
C) Maternal aggression
D) Irritable aggression
A) Premeditated aggression
B) Predatory aggression
C) Maternal aggression
D) Irritable aggression
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49
Describe the synthesis of serotonin and explain why tryptophan levels in the brain increase after consumption of a high-carbohydrate, low-protein meal.
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50
Explain the primary mechanism responsible for termination of serotonergic transmission and name an important class of drugs that acts on that mechanism.
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51
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)?
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52
Name the major serotonin cell clusters in the brainstem and describe their projection pathways.
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53
Why are cats the subject of choice in studies of firing patterns of dorsal raphe nucleus neurons? Describe the changes in firing of serotonergic neurons in the DRN of cats during different behavioral states.
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54
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.
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55
Explain what makes 5-HT3 receptors different from other serotonin receptors. Identify one important therapeutic use of 5-HT3 receptor antagonists.
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56
How does 5-HT, which travels to the arcuate nucleus from DRN and MRN projections, suppress appetite and affect an animal's food-seeking behavior?
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57
Explain how techniques of genetic engineering have contributed to our understanding of the behavioral and physiological functions of the serotonergic system.
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58
What are the three major approaches to the study of the relationship between 5-HT and aggression in humans? What have these approaches showed us about the link between 5-HT and aggression?
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59
Explain how researchers determined that the anxiety-regulating 5-HT1A receptors are postsynaptic. What was the role of the stria terminalis (BNST) in this determination?
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60
Where does gut serotonin come from, what triggers its release, and what is its function?
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