Neurohumoral transmission in CNS: histamine, serotonin, dopamine, GABA, glutamate, glycine MCQs With Answer

Introduction:
This quiz set explores neurohumoral transmission in the CNS, focusing on histamine, serotonin, dopamine, GABA, glutamate, and glycine — key neurotransmitters with distinct synthesis, receptors, transporters, and pharmacology. Designed for M.Pharm students, the questions probe receptor subtypes, intracellular signaling, synaptic handling (synthesis, vesicular transporters, reuptake, metabolism), and clinically relevant drugs and mechanisms. Expect items on functional localization (raphe, substantia nigra, tuberomammillary nucleus), excitatory/inhibitory balance, excitotoxicity, and therapeutic modulation (SSRIs, antipsychotics, benzodiazepines, NMDA modulators). This focused exercise emphasizes mechanistic understanding, drug targets, and pathophysiological implications important for advanced pharmacology and rational drug design.

Q1. Which enzyme is directly responsible for decarboxylation of 5-hydroxytryptophan to serotonin in serotonergic neurons?

• Aromatic L-amino acid decarboxylase
• Monoamine oxidase A
• Tryptophan hydroxylase
• Catechol-O-methyltransferase

Correct Answer: Aromatic L-amino acid decarboxylase

Q2. The principal histaminergic neurons of the brain originate from which nucleus?

• Locus coeruleus
• Tuberomammillary nucleus of the hypothalamus
• Dorsal raphe nucleus
• Ventral tegmental area

Correct Answer: Tuberomammillary nucleus of the hypothalamus

Q3. Which serotonin receptor subtype is a ligand-gated ion channel rather than a G-protein coupled receptor?

• 5-HT1A
• 5-HT2A
• 5-HT3
• 5-HT6

Correct Answer: 5-HT3

Q4. Which transporter is primarily responsible for vesicular storage of monoamines including dopamine and serotonin?

• VMAT2 (vesicular monoamine transporter 2)
• SERT (serotonin transporter)
• DAT (dopamine transporter)
• EAAT2 (excitatory amino acid transporter 2)

Correct Answer: VMAT2 (vesicular monoamine transporter 2)

Q5. Dopamine D2 receptors predominantly couple to which G-protein class and downstream effect?

• Gs, increased cAMP
• Gi/o, decreased cAMP and opening of GIRK channels
• Gq, activation of phospholipase C
• Tyrosine kinase receptor, MAPK activation

Correct Answer: Gi/o, decreased cAMP and opening of GIRK channels

Q6. Which enzyme metabolizes dopamine and is a major target in Parkinson’s disease therapy alongside MAO-B inhibitors?

• Aromatic L-amino acid decarboxylase
• Catechol-O-methyltransferase (COMT)
• DOPA decarboxylase
• Acetylcholinesterase

Correct Answer: Catechol-O-methyltransferase (COMT)

Q7. GABA-A receptor positive allosteric modulators (e.g., benzodiazepines) primarily enhance which ion conductance?

• Voltage-gated sodium channels
• Chloride ion conductance through the GABA-A receptor channel
• NMDA receptor-mediated calcium influx
• Potassium leak channels

Correct Answer: Chloride ion conductance through the GABA-A receptor channel

Q8. Activation of NMDA receptors requires which of the following co-agonists at its glycine site for full activation?

• GABA
• D-serine or glycine
• Acetylcholine
• Histamine

Correct Answer: D-serine or glycine

Q9. Which of the following is the primary reuptake transporter for serotonin at presynaptic terminals?

• SERT (serotonin transporter)
• VMAT2
• NET (norepinephrine transporter)
• vGlut1

Correct Answer: SERT (serotonin transporter)

Q10. Strychnine toxicity produces convulsions by antagonizing which inhibitory neurotransmitter receptor in the spinal cord?

• GABA-B receptor
• Glycine receptor
• GABA-A receptor
• NMDA receptor

Correct Answer: Glycine receptor

Q11. Which glutamate receptor subtype is most directly associated with synaptic plasticity and calcium influx critical for LTP?

• AMPA receptor
• NMDA receptor
• Kainate receptor
• mGluR2 (metabotropic)

Correct Answer: NMDA receptor

Q12. Which drug class works by inhibiting reuptake of serotonin and is commonly used as first-line antidepressants?

• MAO inhibitors
• SSRIs (selective serotonin reuptake inhibitors)
• Typical antipsychotics
• Benzodiazepines

Correct Answer: SSRIs (selective serotonin reuptake inhibitors)

Q13. Which histamine receptor subtype functions as an autoreceptor on histaminergic neurons regulating histamine release and is a target for wake-promoting drugs when antagonized?

• H1 receptor
• H2 receptor
• H3 receptor
• H4 receptor

Correct Answer: H3 receptor

Q14. Reserpine produces depletion of monoamines by acting on which presynaptic mechanism?

• Blocking SERT and DAT transporters
• Inhibiting monoamine oxidase
• Inhibiting VMAT leading to impaired vesicular storage
• Antagonizing postsynaptic receptors

Correct Answer: Inhibiting VMAT leading to impaired vesicular storage

Q15. Which of the following statements about GABA-B receptors is correct?

• They are ionotropic chloride channels mediating fast inhibition
• They are metabotropic G-protein coupled receptors that inhibit adenylate cyclase
• They are ligand-gated sodium channels that depolarize neurons
• They are presynaptic transporters for GABA reuptake

Correct Answer: They are metabotropic G-protein coupled receptors that inhibit adenylate cyclase

Q16. Which transporter is responsible for high-affinity reuptake of glutamate into astrocytes to prevent excitotoxicity?

• SERT
• EAAT2 (GLT-1)
• vGlut2
• GAT-1

Correct Answer: EAAT2 (GLT-1)

Q17. Atypical antipsychotics exert therapeutic effects in schizophrenia partly by antagonizing which dopamine receptor subtype centrally?

• D1 receptor
• D2 receptor
• D4 receptor only
• D5 receptor

Correct Answer: D2 receptor

Q18. Which pharmacological agent is a competitive benzodiazepine-site antagonist used to reverse benzodiazepine overdose?

• Flumazenil
• Diazepam
• Baclofen
• Tiagabine

Correct Answer: Flumazenil

Q19. Which statement best describes the role of glycine in excitatory NMDA receptor function in the CNS?

• Glycine is an inhibitory neurotransmitter and has no role at NMDA receptors
• Glycine competes with glutamate at the NMDA glutamate-binding site
• Glycine serves as an obligatory co-agonist at the NMDA receptor glycine-binding site enhancing channel opening
• Glycine blocks NMDA receptor-associated calcium influx

Correct Answer: Glycine serves as an obligatory co-agonist at the NMDA receptor glycine-binding site enhancing channel opening

Q20. Which of the following best characterizes the action of selective MAO-B inhibitors like selegiline in Parkinson’s disease?

• They increase central serotonin by blocking MAO-A only
• They preferentially inhibit MAO-B, reducing dopamine breakdown and prolonging L-DOPA effects
• They inhibit VMAT2 to deplete dopamine stores
• They are direct dopamine D2 receptor agonists

Correct Answer: They preferentially inhibit MAO-B, reducing dopamine breakdown and prolonging L-DOPA effects

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