STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage &
release
Stem
A 32-year-old woman with major depressive disorder has had
partial response to an SSRI; she reports persistent anergia and
poor motivation despite 8 weeks of treatment. You're
considering adding a medication that increases synaptic
dopamine availability by reducing vesicular monoamine
sequestration in presynaptic terminals. Which mechanism best
matches that augmentation strategy?
,Options
A. Inhibit vesicular monoamine transporter (VMAT) to reduce
vesicular storage and increase cytosolic dopamine available for
reverse transport.
B. Block dopamine D2 receptors to upregulate presynaptic
synthesis via feedback disinhibition.
C. Inhibit monoamine oxidase (MAO) to prevent enzymatic
breakdown within synaptic cleft.
D. Activate presynaptic α2-autoreceptors to increase dopamine
release.
Correct answer
A
Rationales
Correct (A): Inhibiting VMAT reduces vesicular sequestration of
monoamines, increasing cytosolic dopamine that can be
released nonvesicularly or reverse-transported — increasing
extracellular dopamine. Stahl describes VMAT’s role in vesicular
storage and how altering vesicular sequestration changes
transmitter availability. This matches augmentation for residual
motivational symptoms.
Incorrect (B): Blocking D2 receptors reduces postsynaptic
signaling and may increase presynaptic firing acutely, but it does
not increase vesicular dopamine storage or cytosolic dopamine
availability as VMAT inhibition does. Mechanistically misaligned.
Incorrect (C): MAO inhibition reduces intracellular enzymatic
breakdown, increasing overall monoamine levels, but the
,mechanism is enzymatic blockade, not vesicular sequestration
alteration; it also carries broader safety/interaction issues.
Incorrect (D): Activating presynaptic α2-autoreceptors typically
reduces neurotransmitter release (negative feedback), so this
would decrease—not increase—dopamine release.
Teaching point
VMAT inhibition raises cytosolic monoamines by reducing
vesicular sequestration — increases extracellular dopamine
availability.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Reuptake transporters
& synaptic clearance
Stem
A 45-year-old man with generalized anxiety disorder is
intolerant of serotonergic activation (anxiety/agitation) on an
SSRI. You consider switching to a drug that preferentially
increases synaptic norepinephrine over serotonin by blocking
its presynaptic transporter. Which transporter selectivity best
explains a medication that increases synaptic NE more than 5-
HT?
, Options
A. High affinity blockade of the norepinephrine transporter
(NET) with low affinity for the serotonin transporter (SERT).
B. High affinity blockade of SERT with low affinity for NET.
C. Blockade of the vesicular monoamine transporter (VMAT) —
nonselective.
D. Inhibition of monoamine oxidase A (MAO-A) selectively in
postsynaptic neurons.
Correct answer
A
Rationales
Correct (A): Blocking NET selectively increases synaptic
norepinephrine because NET is the principal mechanism for NE
clearance; Stahl emphasizes transporter selectivity determines
which synaptic monoamine is preferentially raised. This can be
beneficial when activation from increased serotonin is not
tolerated.
Incorrect (B): SERT blockade preferentially raises serotonin and
would likely worsen serotonergic activation symptoms.
Incorrect (C): VMAT blockade affects storage of multiple
monoamines and is not a strategy for selective NE increase.
Incorrect (D): MAO-A inhibition increases intracellular
monoamines broadly and is not a selective transporter
blockade; it also acts intracellularly, not on reuptake clearance
mechanisms.
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage &
release
Stem
A 32-year-old woman with major depressive disorder has had
partial response to an SSRI; she reports persistent anergia and
poor motivation despite 8 weeks of treatment. You're
considering adding a medication that increases synaptic
dopamine availability by reducing vesicular monoamine
sequestration in presynaptic terminals. Which mechanism best
matches that augmentation strategy?
,Options
A. Inhibit vesicular monoamine transporter (VMAT) to reduce
vesicular storage and increase cytosolic dopamine available for
reverse transport.
B. Block dopamine D2 receptors to upregulate presynaptic
synthesis via feedback disinhibition.
C. Inhibit monoamine oxidase (MAO) to prevent enzymatic
breakdown within synaptic cleft.
D. Activate presynaptic α2-autoreceptors to increase dopamine
release.
Correct answer
A
Rationales
Correct (A): Inhibiting VMAT reduces vesicular sequestration of
monoamines, increasing cytosolic dopamine that can be
released nonvesicularly or reverse-transported — increasing
extracellular dopamine. Stahl describes VMAT’s role in vesicular
storage and how altering vesicular sequestration changes
transmitter availability. This matches augmentation for residual
motivational symptoms.
Incorrect (B): Blocking D2 receptors reduces postsynaptic
signaling and may increase presynaptic firing acutely, but it does
not increase vesicular dopamine storage or cytosolic dopamine
availability as VMAT inhibition does. Mechanistically misaligned.
Incorrect (C): MAO inhibition reduces intracellular enzymatic
breakdown, increasing overall monoamine levels, but the
,mechanism is enzymatic blockade, not vesicular sequestration
alteration; it also carries broader safety/interaction issues.
Incorrect (D): Activating presynaptic α2-autoreceptors typically
reduces neurotransmitter release (negative feedback), so this
would decrease—not increase—dopamine release.
Teaching point
VMAT inhibition raises cytosolic monoamines by reducing
vesicular sequestration — increases extracellular dopamine
availability.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Reuptake transporters
& synaptic clearance
Stem
A 45-year-old man with generalized anxiety disorder is
intolerant of serotonergic activation (anxiety/agitation) on an
SSRI. You consider switching to a drug that preferentially
increases synaptic norepinephrine over serotonin by blocking
its presynaptic transporter. Which transporter selectivity best
explains a medication that increases synaptic NE more than 5-
HT?
, Options
A. High affinity blockade of the norepinephrine transporter
(NET) with low affinity for the serotonin transporter (SERT).
B. High affinity blockade of SERT with low affinity for NET.
C. Blockade of the vesicular monoamine transporter (VMAT) —
nonselective.
D. Inhibition of monoamine oxidase A (MAO-A) selectively in
postsynaptic neurons.
Correct answer
A
Rationales
Correct (A): Blocking NET selectively increases synaptic
norepinephrine because NET is the principal mechanism for NE
clearance; Stahl emphasizes transporter selectivity determines
which synaptic monoamine is preferentially raised. This can be
beneficial when activation from increased serotonin is not
tolerated.
Incorrect (B): SERT blockade preferentially raises serotonin and
would likely worsen serotonergic activation symptoms.
Incorrect (C): VMAT blockade affects storage of multiple
monoamines and is not a strategy for selective NE increase.
Incorrect (D): MAO-A inhibition increases intracellular
monoamines broadly and is not a selective transporter
blockade; it also acts intracellularly, not on reuptake clearance
mechanisms.
