Psychopathopharmacology 1 MSN 671 quiz 3

Correct Answer:

D. Nitric oxide

Explanation:

Retrograde neurotransmitters are signaling molecules produced by the postsynaptic neuron that travel back to the presynaptic terminal to regulate neurotransmitter release. Nitric oxide (NO) is the classic example: it is synthesized on demand in the postsynaptic neuron and diffuses rapidly across membranes to modulate presynaptic activity. Endocannabinoids (e.g., anandamide, 2-AG) are also important retrograde messengers, but nitric oxide is the prototypical gaseous retrograde neurotransmitter.

Why Other Options Are Wrong:

A. GABA

This is incorrect because GABA is a classical inhibitory neurotransmitter released from presynaptic neurons, not a retrograde signal.

B. Galanin

This is incorrect because galanin is a neuropeptide that acts as a conventional transmitter/modulator, not a retrograde messenger.

C. Histamine

This is incorrect because histamine functions as a neuromodulator in arousal, attention, and immune responses but does not serve as a retrograde neurotransmitter.

Correct Answer:

C: Sodium Pump

Explanation:

Monoamine reuptake transporters (for dopamine, norepinephrine, and serotonin) use the sodium gradient to drive neurotransmitter reuptake into presynaptic terminals. This gradient is maintained by the Na⁺/K⁺-ATPase pump (sodium pump), which actively pumps sodium out of the cell and potassium in. The energy stored in this electrochemical sodium gradient is then harnessed by monoamine transporters to move neurotransmitters back into the neuron against their concentration gradient.

Why Other Options Are Wrong:

A: Calcium Pump

This is incorrect because calcium pumps regulate intracellular calcium for processes like neurotransmitter release but do not power monoamine reuptake.

B: Potassium Pump

This is incorrect because there is no independent potassium pump that directly drives monoamine transport. Potassium movement is part of the Na⁺/K⁺ pump cycle, but sodium is the primary driving force.

D: Proton Pump

This is incorrect because proton pumps generate proton gradients mainly in organelles like lysosomes and synaptic vesicles, not in presynaptic reuptake from the synaptic cleft.

Correct Answer:

B: Cocaine has the same actions at the dopamine transporter as methylphenidate

Explanation:

Cocaine and methylphenidate both act by blocking the dopamine transporter (DAT), which prevents dopamine reuptake into the presynaptic neuron and increases extracellular dopamine. Importantly, neither cocaine nor methylphenidate are taken up into the neuron via the transporter. Amphetamine, in contrast, is transported into the neuron and then reverses the transporter, actively pushing dopamine out of the presynaptic terminal. Thus, cocaine’s pharmacological profile matches methylphenidate, not amphetamine.

Why Other Options Are Wrong:

A: Cocaine has the same actions at the dopamine transporter as amphetamine

This is incorrect because amphetamine enters the neuron via DAT and causes reverse transport, releasing dopamine into the synapse—a mechanism different from simple blockade.

C: A and B

This is incorrect because cocaine only shares its mechanism with methylphenidate, not with amphetamine.

D: Neither A or B

This is incorrect because cocaine clearly shares its mechanism of action with methylphenidate as a DAT blocker.

Correct Answer:

C. Serotonin 2A recept

Explanation:

The serotonin 2A (5-HT2A) receptor is the principal binding site for hallucinogens such as LSD, psilocybin, and MDMA. Activation of these receptors in the cortex alters perception, cognition, and mood, producing hallucinations and psychotic-like symptoms. This receptor is strongly implicated in the pathophysiology of psychosis and is also a target for many atypical antipsychotics, which block 5-HT2A receptors.

Why Other Options Are Wrong:

A. GABA-A receptor

This is incorrect because GABA-A receptors mediate inhibitory neurotransmission and are targeted by drugs like benzodiazepines and alcohol, not hallucinogens.

B. Cannabinoid 1 receptor

This is incorrect because cannabinoid receptors are activated by THC and synthetic cannabinoids, producing different effects such as relaxation, altered perception, and appetite stimulation, but they are not the main hallucinogen binding site.

D. Serotonin 2C receptor

This is incorrect because while 5-HT2C receptors modulate appetite, mood, and anxiety, they are not the primary receptor mediating hallucinogen-induced psychotic-like effects—the 5-HT2A receptor is central.

Correct Answer:

B. Triggering signaling pathways

Explanation:

G proteins act as molecular switches in the G protein-coupled receptor (GPCR) pathway. When a ligand binds to a GPCR, the receptor activates an associated G protein by exchanging GDP for GTP. The activated G protein then goes on to trigger intracellular signaling pathways, which may include stimulating or inhibiting adenylate cyclase, activating phospholipase C, or regulating ion channels. Thus, its central role is initiating diverse downstream effects.

Why Other Options Are Wrong:

A. Inhibiting adenylate cyclase

This is incorrect because this is only one possible action of the Gi type of G proteins, not the universal role of all G proteins.

C. Activating phospholipase C

This is incorrect because this is a specific function of Gq proteins, not the general role of all G proteins.

D. Opening ion channels

This is incorrect because some G proteins (like Gβγ subunits) can open ion channels, but this is not their primary or overall role.

Correct Answer:

A. 5HT2C antagonism

Explanation:

While fluoxetine is primarily an SSRI (serotonin reuptake inhibitor), its early energizing effects are largely attributed to 5HT2C antagonism. The 5HT2C receptor normally inhibits dopamine and norepinephrine release in the prefrontal cortex. By blocking this receptor, fluoxetine disinhibits dopamine and norepinephrine release, leading to improvements in energy, attention, and cognition within days—much faster than the delayed mood-elevating effects from serotonin reuptake inhibition.

Why Other Options Are Wrong:

B. Norepi reuptake inhibition

This is incorrect because fluoxetine is not a norepinephrine reuptake inhibitor. Other antidepressants (e.g., SNRIs, TCAs) provide this effect, but fluoxetine does not significantly block norepinephrine transporters.

C. Serotonin reuptake inhibition

This is incorrect as the explanation for the rapid energizing effect. While fluoxetine does inhibit serotonin reuptake, those changes take weeks to translate into clinical mood improvement. The patient’s immediate boost in energy and cognition is better explained by 5HT2C antagonism.

Correct Answer:

B. Mesolimbic dopamine pathway

Explanation:

The mesolimbic dopamine pathway, projecting from the ventral tegmental area (VTA) to the nucleus accumbens, is considered the brain’s pleasure and reward center. Activation of this pathway underlies the experience of reward, reinforcement, and motivation, and it plays a central role in addiction and reinforcement learning. Dopamine release in the nucleus accumbens is especially critical for the sensation of pleasure.

Why Other Options Are Wrong:

A. Cortico-striatal-thalamic-cortical loop

This is incorrect because this loop is more involved in motor control, habits, and obsessive-compulsive behaviors rather than direct mediation of pleasure.

C. Mesocortical dopamine pathway

This is incorrect because the mesocortical pathway projects from the VTA to the prefrontal cortex and is primarily involved in cognition, attention, and regulation of affect—not the sensation of pleasure.

D. None of the above

This is incorrect because the mesolimbic dopamine pathway is well established as the primary pleasure and reward pathway in the brain.

Correct Answer:

B. Resensitization of nicotinic receptors

Explanation:

Nicotine binds to nicotinic acetylcholine receptors (nAChRs) in the brain, causing receptor activation and dopamine release, which produces reinforcement. After nicotine exposure, nAChRs become desensitized and stop responding despite nicotine being present. Over time (about every 1–2 hours), the receptors resensitize, becoming responsive again. This resensitization drives craving and withdrawal because the brain seeks nicotine to re-activate the now-sensitive receptors, creating the cycle of dependence.

Why Other Options Are Wrong:

A. Desensitization of nicotinic receptors

This is incorrect because desensitization occurs right after smoking, not when cravings emerge. Cravings arise when receptors resensitize.

C. Desensitization of muscarinic receptors

This is incorrect because muscarinic acetylcholine receptors are not the primary target of nicotine in addiction. Nicotine acts on nicotinic receptors, not muscarinic ones.

D. Resensitization of muscarinic receptors

This is incorrect because muscarinic receptors are not central to nicotine craving and withdrawal. The addiction mechanism involves nicotinic receptor cycles, not muscarinic receptor activity.

Correct Answer:

C. Benign Neutropenia

Explanation:

Clozapine carries a risk of agranulocytosis, so prescribers monitor the absolute neutrophil count (ANC) before and during treatment. Some African American patients may have benign ethnic neutropenia (BEN) — a genetic variation leading to lower baseline neutrophil counts without an increased risk of infection. This can hinder initiation of clozapine because standard ANC cutoffs may falsely exclude these patients. Adjusted guidelines now allow for BEN, but prescribers must be aware of this factor before ruling out clozapine.

Why Other Options Are Wrong:

A. Low plasma dimension

This is incorrect because there is no recognized genetic factor called "low plasma dimension" influencing clozapine use.

B. Low Seizure Threshold

This is incorrect because clozapine does lower the seizure threshold at high doses, but this effect is not a specific genetic factor tied to African Americans.

D. None

This is incorrect because benign neutropenia is a real genetic factor in African Americans that impacts clozapine initiation.