Psychopathopharmacology 1 MSN 671 quiz 3

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:

C. Decreases GABA and increases glutamate

Explanation:

Alcohol enhances GABA-A receptor activity in many brain regions, but in the ventral tegmental area (VTA), its net effect is to reduce GABAergic inhibition of dopamine neurons. This disinhibition allows dopamine neurons to fire more readily. Alcohol also increases glutamatergic excitation onto these dopamine neurons. Together, decreased GABA and increased glutamate in the VTA lead to enhanced dopamine release in the nucleus accumbens, reinforcing alcohol’s rewarding effects.

Why Other Options Are Wrong:

A. Increases GABA and decreases glutamate

This is incorrect because increasing GABA and reducing glutamate would suppress dopamine neuron firing, opposite to alcohol’s rewarding effects.

B. Increases both GABA and glutamate

This is incorrect because while alcohol increases glutamate drive, its main effect on GABA in the VTA is a reduction in inhibition of dopamine neurons, not an increase.

D. Decreases both GABA and glutamate

This is incorrect because alcohol does decrease GABA inhibition but simultaneously increases glutamate excitation, not decrease it.

Correct Answer:

A. Han Chinese and HLA-B*15:02

Explanation:

Han Chinese individuals have a significantly increased risk of developing Stevens-Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN) when treated with carbamazepine if they carry the HLA-B*15:02 allele. This allele is strongly associated with severe cutaneous adverse reactions to carbamazepine, and screening is recommended before initiating therapy in populations with high prevalence, such as Han Chinese, Thai, and other Southeast Asian groups.

Why Other Options Are Wrong:

B. African American and HLA-B15:02

This is incorrect because while African Americans may carry other HLA risk alleles, **HLA-B15:02 is rare in this population**, making the risk much lower than in Han Chinese or Southeast Asians.

C. White American and HLA-B15:02

This is incorrect because the prevalence of **HLA-B15:02 in White Americans is extremely low**, so carbamazepine-induced SJS/TEN is not strongly linked to this allele in this population.

D. Hispanic American and HLA-B15:02

This is incorrect because Hispanic populations also have a low frequency of HLA-B15:02, so the genetic risk is not comparable to Han Chinese or other Asian groups.

Correct Answer:

A. Ketamine

Explanation:

Ketamine, an NMDA receptor antagonist originally used as an anesthetic, has been found effective in treating treatment-resistant depression and rapidly reducing suicidal thoughts. Unlike traditional antidepressants that may take weeks to work, ketamine produces effects within hours. It is often administered intravenously in specialized clinics, and a related formulation, esketamine (Spravato®), is FDA-approved as a nasal spray for treatment-resistant depression.

Why Other Options Are Wrong:

B. Propofol

This is incorrect because propofol is an intravenous anesthetic used for induction and maintenance of anesthesia. It is not used in psychiatric treatment for depression or suicidality.

C. Hydroxyzine

This is incorrect because hydroxyzine is an antihistamine with sedative and anxiolytic properties. It may reduce anxiety but is not indicated for resistant depression or suicidal ideation.

D. Valium

This is incorrect because Valium (diazepam) is a benzodiazepine used for anxiety, muscle spasms, and seizures. It does not treat depression or suicidal thoughts and carries risks of dependence.

Correct Answer:

C. A and B

Explanation:

A partial agonist binds to the same receptor as a full agonist but produces a lower maximal response. When neurotransmission is deficient, partial agonists provide enough receptor activity to increase signaling (net agonism). When neurotransmission is excessive, they compete with full agonists for receptor binding but produce less activation, effectively reducing signaling (net antagonism). This stabilizing effect is why partial agonists are often described as “functional stabilizers” of neurotransmission.

Why Other Options Are Wrong:

A. Net agonism when neurotransmission is deficient

This is incomplete because partial agonists can also exert antagonistic effects under conditions of excess neurotransmission, not just agonism when deficient.

B. Net antagonism when neurotransmission is excessive

This is also incomplete. While true for high neurotransmission, it fails to account for the agonist effect when transmission is low.

D. Neither A nor B

This is incorrect because partial agonists clearly demonstrate both agonistic and antagonistic properties depending on the state of neurotransmission.

Correct Answer:

A. Phase I

Explanation:

Phase I clinical trials are the first stage of testing in humans and typically involve a small group (20–100) of healthy volunteers. The primary goal is to evaluate safety, tolerability, dosage ranges, and pharmacokinetics of the drug. This phase answers the question: Is the drug safe in humans?

Why Other Options Are Wrong:

B. Phase IV

This is incorrect because Phase IV occurs after FDA approval, focusing on post-marketing surveillance to monitor long-term safety and rare adverse effects in the general population.

C. Phase III

This is incorrect because Phase III involves large randomized controlled trials in patients with the target condition to confirm efficacy, monitor side effects, and compare with standard treatments.

D. Phase II

This is incorrect because Phase II involves a larger group of patients with the disease to test efficacy and further assess safety, not healthy volunteers.

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: Hypofunctioning NMDA receptors

Explanation:

The glutamate hypothesis, specifically NMDA receptor hypofunction, is the leading explanation for schizophrenia today. NMDA antagonists like ketamine and PCP can mimic both positive and negative symptoms of the disorder. Hypofunction of NMDA receptors on inhibitory interneurons disrupts excitatory–inhibitory balance, contributing to abnormal dopamine signaling.

Why Other Options Are Wrong:

A: Hyperfunctioning NMDA receptors

This is incorrect because schizophrenia is linked to reduced, not increased, NMDA receptor activity.

C: Hyperdopaminergic activity in mesolimbic pathways

This describes the older dopamine hypothesis of schizophrenia, which explains positive symptoms well, but it does not fully account for negative and cognitive symptoms.

D: Hypodopaminergic activity in mesocortical pathways

This is partially true since mesocortical dopamine deficits are linked to negative symptoms and cognitive dysfunction. However, the broader unifying hypothesis is NMDA receptor hypofunction, which influences both dopamine pathways.

Correct Answer:

A. Dopamine in the prefrontal cortex

Explanation:

Volume neurotransmission refers to neurotransmitter release that is not restricted to the synaptic cleft but instead diffuses over a wider area, influencing multiple neurons. In the prefrontal cortex, dopamine terminals often lack classic synaptic specializations. Instead, dopamine is released into the extracellular space, where it diffuses and binds to receptors located away from release sites. This is a prime example of volume transmission.

Why Other Options Are Wrong:

B. Dopamine in the striatum

This is incorrect because dopamine release in the striatum occurs primarily at well-defined synaptic junctions with precise wiring, making it a clear case of wired transmission rather than volume transmission.

C. Norepinephrine in the prefrontal cortex

This is incorrect because norepinephrine in the prefrontal cortex can have modulatory effects, but it is dopamine that is specifically recognized in the literature as the classic example of volume transmission in this region.

D. Norepinephrine in the striatum

This is incorrect because norepinephrine projections to the striatum are sparse, and where present, they do not serve as the hallmark example of volume transmission.