STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Synaptic Architecture &
Directionality
Stem (PMHNP-level, 2–4 sentences)
A 46-year-old patient with treatment-resistant depression has
prominent psychomotor slowing and bradykinesia on exam. You
consider whether abnormal neural circuit firing patterns
affecting output neurons could explain the motor signs and
whether targeting presynaptic vs postsynaptic mechanisms
would differ in effect. Based on the architecture of chemical
neurotransmission, which intervention is most likely to directly
reduce excessive presynaptic neurotransmitter release onto
downstream motor neurons?
,Options
A. Blockade of presynaptic voltage-gated Ca²⁺ channels
B. Blockade of postsynaptic G-protein–coupled receptors on
motor neurons
C. Positive allosteric modulation of postsynaptic ionotropic
receptors
D. Inhibition of postsynaptic second-messenger kinases
Correct Answer
A
Rationales
• Correct (A): Blocking presynaptic voltage-gated Ca²⁺
channels decreases the Ca²⁺ influx required for vesicular
neurotransmitter release, directly reducing transmitter
release onto downstream neurons. Stahl emphasizes
presynaptic Ca²⁺ entry as the trigger for exocytosis, so this
mechanism most directly lowers synaptic drive.
• Incorrect (B): Blocking postsynaptic GPCRs modulates
postsynaptic responsiveness but does not reduce
presynaptic release. It changes receptor signaling rather
than vesicular exocytosis.
• Incorrect (C): Positive allosteric modulation of postsynaptic
ionotropic receptors would increase postsynaptic
responses and worsen downstream activation.
• Incorrect (D): Inhibiting postsynaptic kinases affects
intracellular signaling and receptor regulation downstream
, of receptor activation but does not acutely reduce
presynaptic release.
Teaching Point (≤20 words)
Presynaptic Ca²⁺ influx is the proximal trigger for
neurotransmitter release; blocking it lowers synaptic output.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular Packaging &
VMAT
Stem
A middle-aged patient on multiple psychotropic agents
develops extrapyramidal symptoms and you suspect excessive
cytosolic dopaminergic activity with oxidative metabolites.
Which presynaptic mechanism, if enhanced, would most
directly reduce cytosolic monoamine breakdown and lower
formation of toxic metabolites?
Options
A. Increased VMAT-mediated vesicular uptake of cytosolic
monoamines
B. Increased plasma membrane monoamine transporter
(DAT/SERT/NET) activity
, C. Inhibition of vesicular proton gradient (collapse of vesicular
pH)
D. Upregulation of monoamine oxidase (MAO) activity
Correct Answer
A
Rationales
• Correct (A): Enhancing VMAT function sequesters
monoamines into vesicles, reducing cytosolic
concentration available to MAO and thereby decreasing
oxidative metabolite formation. Stahl explains vesicular
sequestration as neuroprotective by limiting cytosolic
monoamine exposure to degradative enzymes.
• Incorrect (B): Increasing plasma membrane transporter
uptake shuttles extracellular transmitter back into cytosol,
potentially raising cytosolic substrate for MAO and
increasing metabolite formation.
• Incorrect (C): Collapsing vesicular pH impairs VMAT
loading, increasing cytosolic monoamines and oxidative
metabolism—opposite of desired effect.
• Incorrect (D): Upregulating MAO directly increases
breakdown and toxic metabolite production.
Teaching Point
VMAT sequestration protects neurons by removing
monoamines from the cytosol and limiting MAO-mediated
oxidation.
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Synaptic Architecture &
Directionality
Stem (PMHNP-level, 2–4 sentences)
A 46-year-old patient with treatment-resistant depression has
prominent psychomotor slowing and bradykinesia on exam. You
consider whether abnormal neural circuit firing patterns
affecting output neurons could explain the motor signs and
whether targeting presynaptic vs postsynaptic mechanisms
would differ in effect. Based on the architecture of chemical
neurotransmission, which intervention is most likely to directly
reduce excessive presynaptic neurotransmitter release onto
downstream motor neurons?
,Options
A. Blockade of presynaptic voltage-gated Ca²⁺ channels
B. Blockade of postsynaptic G-protein–coupled receptors on
motor neurons
C. Positive allosteric modulation of postsynaptic ionotropic
receptors
D. Inhibition of postsynaptic second-messenger kinases
Correct Answer
A
Rationales
• Correct (A): Blocking presynaptic voltage-gated Ca²⁺
channels decreases the Ca²⁺ influx required for vesicular
neurotransmitter release, directly reducing transmitter
release onto downstream neurons. Stahl emphasizes
presynaptic Ca²⁺ entry as the trigger for exocytosis, so this
mechanism most directly lowers synaptic drive.
• Incorrect (B): Blocking postsynaptic GPCRs modulates
postsynaptic responsiveness but does not reduce
presynaptic release. It changes receptor signaling rather
than vesicular exocytosis.
• Incorrect (C): Positive allosteric modulation of postsynaptic
ionotropic receptors would increase postsynaptic
responses and worsen downstream activation.
• Incorrect (D): Inhibiting postsynaptic kinases affects
intracellular signaling and receptor regulation downstream
, of receptor activation but does not acutely reduce
presynaptic release.
Teaching Point (≤20 words)
Presynaptic Ca²⁺ influx is the proximal trigger for
neurotransmitter release; blocking it lowers synaptic output.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular Packaging &
VMAT
Stem
A middle-aged patient on multiple psychotropic agents
develops extrapyramidal symptoms and you suspect excessive
cytosolic dopaminergic activity with oxidative metabolites.
Which presynaptic mechanism, if enhanced, would most
directly reduce cytosolic monoamine breakdown and lower
formation of toxic metabolites?
Options
A. Increased VMAT-mediated vesicular uptake of cytosolic
monoamines
B. Increased plasma membrane monoamine transporter
(DAT/SERT/NET) activity
, C. Inhibition of vesicular proton gradient (collapse of vesicular
pH)
D. Upregulation of monoamine oxidase (MAO) activity
Correct Answer
A
Rationales
• Correct (A): Enhancing VMAT function sequesters
monoamines into vesicles, reducing cytosolic
concentration available to MAO and thereby decreasing
oxidative metabolite formation. Stahl explains vesicular
sequestration as neuroprotective by limiting cytosolic
monoamine exposure to degradative enzymes.
• Incorrect (B): Increasing plasma membrane transporter
uptake shuttles extracellular transmitter back into cytosol,
potentially raising cytosolic substrate for MAO and
increasing metabolite formation.
• Incorrect (C): Collapsing vesicular pH impairs VMAT
loading, increasing cytosolic monoamines and oxidative
metabolism—opposite of desired effect.
• Incorrect (D): Upregulating MAO directly increases
breakdown and toxic metabolite production.
Teaching Point
VMAT sequestration protects neurons by removing
monoamines from the cytosol and limiting MAO-mediated
oxidation.
