STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Presynaptic release and
autoreceptor regulation
Stem
A 32-year-old woman with recurrent major depressive disorder
partially responded to an SSRI for 8 weeks but reports
persistent anergia and fatigue despite improved mood. She also
reports mild nausea since starting the SSRI. You consider
augmenting to target presynaptic monoamine release rather
than increasing synaptic serotonin directly. Which mechanism
best matches a drug that would increase presynaptic
norepinephrine and dopamine release by reversing their
transporters?
,Options
A. VMAT inhibitor (depletes vesicular monoamines)
B. Monoamine reuptake inhibitor (blocks NET and DAT)
C. Monoamine oxidase inhibitor (inhibits enzymatic
degradation)
D. Substrate-type releaser that reverses monoamine
transporters
Correct answer
D
Rationales
Correct (D): Substrate-type releasers enter presynaptic
terminals via transporters and cause transporter reversal,
increasing nonvesicular release of NE and DA. Stahl explains
transporter reversal as a presynaptic mechanism distinct from
reuptake blockade and VMAT inhibition, producing rapid
increases in extracellular monoamines. This mechanism fits
augmentation when reuptake blockade alone failed to address
energy/motivation symptoms.
A (VMAT inhibitor): VMAT inhibition (e.g., reserpine) depletes
vesicular stores and reduces synaptic monoamines, worsening
anergia. Not appropriate.
B (reuptake inhibitor): Reuptake blockade increases synaptic
monoamines by blocking transporter clearance but does not
actively reverse transporter direction to release additional
cytosolic monoamines.
C (MAOI): MAOI prevents breakdown and raises intracellular
,and extracellular monoamines over time via reduced
metabolism, but it does not reverse transporter direction to
produce immediate presynaptic release.
Teaching point
Transporter-reversing substrates increase extracellular
monoamines by forcing presynaptic release, unlike reuptake
blockers.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage and
VMAT
Stem
A 68-year-old man with Parkinsonism is given a presynaptic
drug that disrupts vesicular monoamine transport. Within
weeks he develops severe depression and anergia. Which
vesicular mechanism explains these neuropsychiatric adverse
effects?
Options
A. Enhanced vesicular refilling leading to increased synaptic
monoamines
B. VMAT inhibition causing cytosolic monoamine depletion and
, reduced synaptic release
C. Increased vesicle fusion probability increasing
neurotransmission
D. Increased postsynaptic receptor sensitivity compensating for
higher synaptic monoamines
Correct answer
B
Rationales
Correct (B): VMAT inhibition prevents sequestration of
monoamines into synaptic vesicles, depleting vesicular stores
and reducing synaptic monoamine release, producing
depressive symptoms. Stahl emphasizes that agents blocking
VMAT reduce synaptic monoamine availability and can cause
depression.
A: The described drug causes decreased, not enhanced,
vesicular refilling.
C: Increased vesicle fusion would increase release; the clinical
picture shows reduced neurotransmission.
D: Postsynaptic receptor sensitivity is a compensatory change
but does not explain an immediate drop in synaptic
monoamines due to VMAT inhibition.
Teaching point
VMAT inhibition depletes vesicular monoamines → reduced
synaptic release and risk of depression.
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Presynaptic release and
autoreceptor regulation
Stem
A 32-year-old woman with recurrent major depressive disorder
partially responded to an SSRI for 8 weeks but reports
persistent anergia and fatigue despite improved mood. She also
reports mild nausea since starting the SSRI. You consider
augmenting to target presynaptic monoamine release rather
than increasing synaptic serotonin directly. Which mechanism
best matches a drug that would increase presynaptic
norepinephrine and dopamine release by reversing their
transporters?
,Options
A. VMAT inhibitor (depletes vesicular monoamines)
B. Monoamine reuptake inhibitor (blocks NET and DAT)
C. Monoamine oxidase inhibitor (inhibits enzymatic
degradation)
D. Substrate-type releaser that reverses monoamine
transporters
Correct answer
D
Rationales
Correct (D): Substrate-type releasers enter presynaptic
terminals via transporters and cause transporter reversal,
increasing nonvesicular release of NE and DA. Stahl explains
transporter reversal as a presynaptic mechanism distinct from
reuptake blockade and VMAT inhibition, producing rapid
increases in extracellular monoamines. This mechanism fits
augmentation when reuptake blockade alone failed to address
energy/motivation symptoms.
A (VMAT inhibitor): VMAT inhibition (e.g., reserpine) depletes
vesicular stores and reduces synaptic monoamines, worsening
anergia. Not appropriate.
B (reuptake inhibitor): Reuptake blockade increases synaptic
monoamines by blocking transporter clearance but does not
actively reverse transporter direction to release additional
cytosolic monoamines.
C (MAOI): MAOI prevents breakdown and raises intracellular
,and extracellular monoamines over time via reduced
metabolism, but it does not reverse transporter direction to
produce immediate presynaptic release.
Teaching point
Transporter-reversing substrates increase extracellular
monoamines by forcing presynaptic release, unlike reuptake
blockers.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage and
VMAT
Stem
A 68-year-old man with Parkinsonism is given a presynaptic
drug that disrupts vesicular monoamine transport. Within
weeks he develops severe depression and anergia. Which
vesicular mechanism explains these neuropsychiatric adverse
effects?
Options
A. Enhanced vesicular refilling leading to increased synaptic
monoamines
B. VMAT inhibition causing cytosolic monoamine depletion and
, reduced synaptic release
C. Increased vesicle fusion probability increasing
neurotransmission
D. Increased postsynaptic receptor sensitivity compensating for
higher synaptic monoamines
Correct answer
B
Rationales
Correct (B): VMAT inhibition prevents sequestration of
monoamines into synaptic vesicles, depleting vesicular stores
and reducing synaptic monoamine release, producing
depressive symptoms. Stahl emphasizes that agents blocking
VMAT reduce synaptic monoamine availability and can cause
depression.
A: The described drug causes decreased, not enhanced,
vesicular refilling.
C: Increased vesicle fusion would increase release; the clinical
picture shows reduced neurotransmission.
D: Postsynaptic receptor sensitivity is a compensatory change
but does not explain an immediate drop in synaptic
monoamines due to VMAT inhibition.
Teaching point
VMAT inhibition depletes vesicular monoamines → reduced
synaptic release and risk of depression.
