MSN 671 : Psychopathopharmacology I -Module 4 quiz 4

Correct Answer:

B. Mesolimbic pathway

Explanation:

Positive symptoms of schizophrenia, including delusions and hallucinations, are strongly associated with dopamine hyperactivity in the mesolimbic pathway. This pathway projects from the ventral tegmental area (VTA) to the nucleus accumbens and other limbic structures, and its overactivation produces the abnormal salience attribution that drives psychosis.

Why Other Options Are Wrong:

A. Nigrostriatal pathway

This is incorrect because the nigrostriatal pathway is primarily involved in motor control. D2 blockade here causes extrapyramidal side effects, not psychotic symptoms.

C. Mesocortical pathway

This is incorrect because mesocortical dopamine hypofunction is associated with negative symptoms (apathy, flat affect) and cognitive impairment, not positive symptoms.

D. Tuberoinfundibular pathway

This is incorrect because this pathway regulates prolactin secretion. D2 blockade here leads to hyperprolactinemia, not hallucinations or delusions.

Correct Answer:

B. Hypodopaminergic activity in the mesocortical pathway

Explanation:

Negative symptoms of schizophrenia—such as apathy, flat affect, social withdrawal, and impaired executive function—are linked to reduced dopamine activity in the mesocortical pathway. This pathway projects from the ventral tegmental area (VTA) to the prefrontal cortex. Insufficient dopamine signaling here leads to deficits in motivation, cognition, and emotional regulation.

Why Other Options Are Wrong:

A. Hyperdopaminergic activity in the mesolimbic pathway

This is incorrect because mesolimbic hyperactivity explains positive symptoms like hallucinations and delusions, not negative symptoms.

C. Hypodopaminergic activity in the nigrostriatal pathway

This is incorrect because dopamine deficiency here causes motor symptoms and extrapyramidal side effects, not schizophrenia’s negative symptoms.

D. Hyperdopaminergic activity in the tuberoinfundibular pathway

This is incorrect because this pathway regulates prolactin release. Hyperactivity here is not associated with schizophrenia but with endocrine imbalance.

Correct Answer:

B. Mu

Explanation:

The mu-opioid receptor is the primary receptor responsible for the euphoric and reinforcing effects of opioids. Activation of mu receptors in the mesolimbic dopamine pathway (particularly in the nucleus accumbens) increases dopamine release, producing the rewarding effects that contribute to opioid abuse and dependence. Mu receptors are also responsible for analgesia, respiratory depression, and constipation.

Why Other Options Are Wrong:

A. Kappa

This is incorrect because kappa receptor activation produces dysphoria and hallucinations, not euphoria.

C. Delta

This is incorrect because delta receptors are involved in mood regulation and analgesia but do not primarily mediate euphoria or reinforcement.

D. Sigma

This is incorrect because sigma receptors are not true opioid receptors; they are associated with psychotomimetic effects, not the rewarding effects of opioids.

Correct Answers:

A. Dopamine hyperactivity at D2 receptors in the mesolimbic/mesostriatal pathway

B. NMDA receptor hypoactivity at GABAergic interneurons with loss of GABAergic inhibition in the prefrontal cortex

C. Serotonin hyperactivity/imbalance at 5HT2A receptors on glutamate neurons in the cerebral cortex

Explanation:

Hallucinations and delusions in psychotic disorders are linked to multiple interacting pathways:

Dopamine hypothesis: Overactivity of dopamine at D2 receptors in the mesolimbic pathway is strongly associated with positive symptoms (hallucinations and delusions).

Glutamate hypothesis: NMDA receptor hypofunction on GABAergic interneurons in the cortex leads to reduced GABAergic inhibition, resulting in cortical disinhibition and downstream dysregulation of dopamine signaling.

Serotonin hypothesis: Excessive 5HT2A receptor stimulation on cortical glutamate neurons contributes to distorted perception and thought, as seen with hallucinogens.

Why Other Option Is Wrong:

D. Epinephrine hyperactivity at D2 receptors in the mesolimbic/nigrostriatal pathway

This is incorrect because epinephrine is not the neurotransmitter driving psychotic symptoms in these circuits. Dopamine, glutamate, and serotonin are the key players.

Correct Answer:

C. Glutamate and glycine

Explanation:

NMDA receptors are a subtype of glutamate receptors that require both glutamate and glycine (or D-serine) to bind for activation. These two act as co-agonists at distinct receptor sites. At resting potential, the channel pore is blocked by magnesium, which prevents ion flow. Depolarization removes this magnesium block, but magnesium is not an activating ligand—it is an inhibitory block. Therefore, true activation depends on glutamate and glycine.

Why Other Options Are Wrong:

A. Glutamate only

This is incorrect because glutamate alone cannot open the NMDA receptor; glycine is also required.

B. Glycine only

This is incorrect because glycine alone cannot activate the receptor without glutamate binding.

D. Glutamate, glycine, and magnesium binding

This is incorrect because magnesium does not activate NMDA receptors; it blocks the ion channel until depolarization removes it.

Correct Answer:

C. Glutamate

Explanation:

Glutamate is the brain’s major excitatory neurotransmitter and is often referred to as the “master switch” because nearly all neurons in the central nervous system can be activated by glutamatergic signaling. It plays a critical role in synaptic plasticity, learning, and memory. Through receptors like NMDA, AMPA, and kainate, glutamate enables fast excitatory neurotransmission and is central to both normal cognition and pathological processes such as excitotoxicity.

Why Other Options Are Wrong:

A. Norepinephrine

This is incorrect because norepinephrine acts as a neuromodulator involved in alertness, arousal, and the fight-or-flight response, but it is not the primary excitatory neurotransmitter.

B. Epinephrine

This is incorrect because epinephrine functions mainly as a hormone in the periphery and has limited neurotransmitter roles in the CNS.

D. Dopamine

This is incorrect because dopamine is a modulatory neurotransmitter involved in reward, motivation, and motor control, but it is not the brain’s major excitatory neurotransmitter.

Correct Answer:

C. Tuberoinfundibular Dopamine Pathway

Explanation:

The tuberoinfundibular pathway projects from the hypothalamus to the pituitary gland and regulates the secretion of prolactin. Normally, dopamine inhibits prolactin release via D2 receptor stimulation. When antipsychotic drugs block D2 receptors in this pathway, dopamine’s inhibitory control is lost, leading to elevated prolactin levels (hyperprolactinemia). Clinically, this can result in galactorrhea, amenorrhea, gynecomastia, and sexual dysfunction in patients receiving antipsychotic therapy.

Why Other Options Are Wrong:

A. Thalamic Dopamine Pathway

This is incorrect because there is no well-defined thalamic dopamine pathway associated with prolactin regulation.

B. Nigrostriatal Dopamine Pathway

This is incorrect because the nigrostriatal pathway is involved in motor control, and its D2 blockade causes extrapyramidal side effects, not hyperprolactinemia.

D. Mesolimbic Dopamine Pathway

This is incorrect because the mesolimbic pathway regulates reward and emotion. D2 blockade here reduces positive symptoms of schizophrenia but does not affect prolactin.

E. Mesocortical Dopamine Pathway

This is incorrect because the mesocortical pathway influences cognition and negative symptoms. Its dysfunction is linked to apathy and impaired executive function, not prolactin regulation.

Correct Answer:

C. Mesocortical and Mesolimbic pathways

Explanation:

Positive and negative symptoms of schizophrenia are explained by dysfunction in two major dopamine pathways. Hyperactivity in the mesolimbic pathway (increased dopamine signaling to the nucleus accumbens) produces positive symptoms such as hallucinations and delusions. Hypoactivity in the mesocortical pathway (reduced dopamine to the prefrontal cortex) contributes to negative symptoms like apathy, reduced motivation, and impaired cognition. These two pathways together form the core of the dopamine hypothesis of schizophrenia.

Why Other Options Are Wrong:

A. Mesolimbic and Nigrostriatal pathways

This is incorrect because the nigrostriatal pathway is involved in movement regulation, and its dysfunction causes extrapyramidal side effects, not schizophrenia’s positive or negative symptoms.

B. Nigrostriatal and Tuberoinfundibular pathways

This is incorrect because these two pathways are not linked to schizophrenia symptoms. The nigrostriatal pathway governs motor control, while the tuberoinfundibular pathway regulates prolactin release.

D. Tuberoinfundibular and Mesocortical pathways

This is incorrect because the tuberoinfundibular pathway is not related to psychotic symptoms. Only the mesocortical pathway among these is relevant, as it contributes to negative and cognitive symptoms.

Correct Answer:

A. Dopamine and norepinephrine

Explanation:

The prefrontal cortex is responsible for executive functions such as attention, working memory, and impulse control. In ADHD, impaired regulation of dopamine and norepinephrine in prefrontal circuits leads to inefficient tuning of information processing. Stimulant medications like methylphenidate and amphetamines improve ADHD symptoms by enhancing both dopamine and norepinephrine signaling in these pathways.

Why Other Options Are Wrong:

B. Dopamine and serotonin

This is incorrect because serotonin primarily modulates mood, sleep, and anxiety, not the executive dysfunction central to ADHD.

C. Norepinephrine and serotonin

This is incorrect because serotonin is not a primary regulator of prefrontal attention circuits. Norepinephrine contributes, but dopamine is equally essential.

D. Dopamine and glutamate

This is incorrect because while glutamate is the brain’s main excitatory neurotransmitter, it is dopamine and norepinephrine specifically that fine-tune prefrontal cortical function in ADHD.