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
autoreceptors and feedback control
Stem
A 32-year-old patient with generalized anxiety reports partial
benefit from a selective reuptake inhibitor but continues to
have persistent anxiety and early morning activation. You
consider adjunct strategies that reduce presynaptic
neurotransmitter release to limit overstimulation during early-
morning peaks. Which mechanism most directly reduces
presynaptic neurotransmitter release via an autoreceptor-
mediated negative feedback loop?
,Options
A. Agonism at presynaptic Gi/o-coupled autoreceptors.
B. Inhibition of vesicular monoamine transporter (VMAT2).
C. Blockade of postsynaptic ionotropic receptors.
D. Inhibition of neurotransmitter reuptake transporters.
Correct answer
A
Rationales
Correct (A): Agonism at presynaptic Gi/o-coupled autoreceptors
(for example, somatodendritic or terminal autoreceptors)
reduces neuronal firing probability and calcium-dependent
release, producing negative feedback on transmitter release.
Stahl emphasizes autoreceptor function as a rapid homeostatic
brake on synaptic output; thus activating these receptors
directly reduces presynaptic release and can blunt morning
hyperactivation.
Incorrect (B): VMAT2 inhibition reduces vesicular storage and
eventually synaptic release, but its action is indirect, slower, and
not mediated by autoreceptor feedback; it can produce broader
depletion rather than tuning release dynamically.
Incorrect (C): Blockade of postsynaptic ionotropic receptors
reduces postsynaptic signaling but does not directly reduce
presynaptic release through feedback autoreceptor
mechanisms.
Incorrect (D): Reuptake inhibition increases synaptic transmitter
,levels, which may indirectly engage autoreceptors but does not
itself constitute activation of autoreceptors to reduce release.
Teaching point (≤20 words)
Autoreceptor agonism provides rapid, presynaptic negative
feedback to reduce neurotransmitter release and limit
activation.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage and
release dynamics
Stem
A 45-year-old patient with severe tardive dyskinesia is being
considered for a pharmacologic strategy that lowers synaptic
monoamine availability by reducing vesicular storage without
directly blocking postsynaptic receptors. Which mechanism is
most consistent with that presynaptic target?
Options
A. VMAT2 inhibition decreasing vesicular monoamine uptake.
B. Postsynaptic GPCR antagonism reducing downstream
signaling.
, C. Increasing neurotransmitter synthesis via precursor loading.
D. Blocking neurotransmitter reuptake transporters.
Correct answer
A
Rationales
Correct (A): VMAT2 inhibitors reduce uptake of monoamines
into synaptic vesicles, decreasing quantal content and resulting
synaptic release; Stahl describes vesicular storage as a crucial
determinant of release and target for decreasing synaptic
monoamines. This presynaptic approach can reduce
hyperkinetic movement syndromes linked to excessive synaptic
dopamine.
Incorrect (B): Postsynaptic GPCR antagonism blocks receptor
signaling but does not reduce vesicular storage or presynaptic
release; it alters response but not presynaptic quantal content.
Incorrect (C): Increasing precursor availability raises synthesis
and would increase, not decrease, vesicular monoamine
content.
Incorrect (D): Reuptake blockade increases extracellular
transmitter by preventing clearance rather than reducing
vesicular stores.
Teaching point (≤20 words)
VMAT2 inhibition lowers vesicular monoamine content and
reduces synaptic release—presynaptic depletion strategy.
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Presynaptic
autoreceptors and feedback control
Stem
A 32-year-old patient with generalized anxiety reports partial
benefit from a selective reuptake inhibitor but continues to
have persistent anxiety and early morning activation. You
consider adjunct strategies that reduce presynaptic
neurotransmitter release to limit overstimulation during early-
morning peaks. Which mechanism most directly reduces
presynaptic neurotransmitter release via an autoreceptor-
mediated negative feedback loop?
,Options
A. Agonism at presynaptic Gi/o-coupled autoreceptors.
B. Inhibition of vesicular monoamine transporter (VMAT2).
C. Blockade of postsynaptic ionotropic receptors.
D. Inhibition of neurotransmitter reuptake transporters.
Correct answer
A
Rationales
Correct (A): Agonism at presynaptic Gi/o-coupled autoreceptors
(for example, somatodendritic or terminal autoreceptors)
reduces neuronal firing probability and calcium-dependent
release, producing negative feedback on transmitter release.
Stahl emphasizes autoreceptor function as a rapid homeostatic
brake on synaptic output; thus activating these receptors
directly reduces presynaptic release and can blunt morning
hyperactivation.
Incorrect (B): VMAT2 inhibition reduces vesicular storage and
eventually synaptic release, but its action is indirect, slower, and
not mediated by autoreceptor feedback; it can produce broader
depletion rather than tuning release dynamically.
Incorrect (C): Blockade of postsynaptic ionotropic receptors
reduces postsynaptic signaling but does not directly reduce
presynaptic release through feedback autoreceptor
mechanisms.
Incorrect (D): Reuptake inhibition increases synaptic transmitter
,levels, which may indirectly engage autoreceptors but does not
itself constitute activation of autoreceptors to reduce release.
Teaching point (≤20 words)
Autoreceptor agonism provides rapid, presynaptic negative
feedback to reduce neurotransmitter release and limit
activation.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage and
release dynamics
Stem
A 45-year-old patient with severe tardive dyskinesia is being
considered for a pharmacologic strategy that lowers synaptic
monoamine availability by reducing vesicular storage without
directly blocking postsynaptic receptors. Which mechanism is
most consistent with that presynaptic target?
Options
A. VMAT2 inhibition decreasing vesicular monoamine uptake.
B. Postsynaptic GPCR antagonism reducing downstream
signaling.
, C. Increasing neurotransmitter synthesis via precursor loading.
D. Blocking neurotransmitter reuptake transporters.
Correct answer
A
Rationales
Correct (A): VMAT2 inhibitors reduce uptake of monoamines
into synaptic vesicles, decreasing quantal content and resulting
synaptic release; Stahl describes vesicular storage as a crucial
determinant of release and target for decreasing synaptic
monoamines. This presynaptic approach can reduce
hyperkinetic movement syndromes linked to excessive synaptic
dopamine.
Incorrect (B): Postsynaptic GPCR antagonism blocks receptor
signaling but does not reduce vesicular storage or presynaptic
release; it alters response but not presynaptic quantal content.
Incorrect (C): Increasing precursor availability raises synthesis
and would increase, not decrease, vesicular monoamine
content.
Incorrect (D): Reuptake blockade increases extracellular
transmitter by preventing clearance rather than reducing
vesicular stores.
Teaching point (≤20 words)
VMAT2 inhibition lowers vesicular monoamine content and
reduces synaptic release—presynaptic depletion strategy.
