Introduction: Screening models for CNS activity are essential tools in preclinical antidepressant research, helping B.Pharm students understand pharmacology, behavioral assays, and translational science. Common screening models—such as the forced swim test, tail suspension test, chronic mild stress, learned helplessness, olfactory bulbectomy, and reserpine reversal—evaluate behavioral and biochemical endpoints that reflect antidepressant-like activity. Knowledge of validity types (face, predictive, construct), neurotransmitter targets, assay limitations, species and strain differences, dosing paradigms, and ethical considerations is crucial for reliable interpretation. Mastery of screening models equips students to design experiments, analyze data, and appreciate drug discovery challenges. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which behavioral assay is most commonly used to screen for acute antidepressant-like activity by measuring immobility time in rodents?
- Forced Swim Test
- Sucrose Preference Test
- Olfactory Bulbectomy
- Chronic Mild Stress
Correct Answer: Forced Swim Test
Q2. The Tail Suspension Test primarily measures which behavioral endpoint as an indicator of antidepressant effect?
- Sucrose consumption
- Latency to feed
- Immobility duration
- Social interaction time
Correct Answer: Immobility duration
Q3. Which model is considered more appropriate to evaluate chronic antidepressant efficacy and anhedonia by reduced pleasure-seeking behavior?
- Forced Swim Test
- Tail Suspension Test
- Sucrose Preference Test
- Reserpine Reversal
Correct Answer: Sucrose Preference Test
Q4. Olfactory bulbectomy in rodents is used as a model for depression because it produces long-lasting behaviors analogous to human depression; which feature best describes its construct validity?
- Immediate response to a single acute drug dose
- Removal of olfactory bulbs models neurobiological changes linked to depression
- Only measures motor deficits unrelated to mood
- Exclusive use in in vitro assays
Correct Answer: Removal of olfactory bulbs models neurobiological changes linked to depression
Q5. Which criterion evaluates how well a screening model predicts clinical efficacy of antidepressants?
- Face validity
- Predictive validity
- Construct validity
- Translational validity
Correct Answer: Predictive validity
Q6. The reserpine reversal test detects antidepressant-like activity by reversing which pharmacological effect of reserpine?
- Excess serotonin release
- Monoamine depletion from synaptic vesicles
- NMDA receptor blockade
- GABAergic overactivation
Correct Answer: Monoamine depletion from synaptic vesicles
Q7. Learned helplessness as a depression model is induced by which experimental manipulation?
- Repeated forced swimming without escape
- Chronic unpredictable mild stressors
- Repeated inescapable electric shocks
- Administration of monoamine oxidase inhibitors
Correct Answer: Repeated inescapable electric shocks
Q8. Which in vivo technique measures extracellular neurotransmitter levels in specific brain regions during screening of antidepressants?
- Receptor autoradiography
- Microdialysis
- Western blotting
- ELISA on plasma
Correct Answer: Microdialysis
Q9. In the forced swim test, a false-positive antidepressant-like effect may result from which confounding factor?
- Reduced locomotor activity
- Increased locomotor activity or stimulation
- Chronic dosing regimen
- Use of inbred strains
Correct Answer: Increased locomotor activity or stimulation
Q10. Which type of validity refers to superficial similarity between animal behavior and human depressive symptoms?
- Face validity
- Predictive validity
- Construct validity
- External validity
Correct Answer: Face validity
Q11. Chronic mild stress (CMS) models depression-like states primarily by producing which measurable change?
- Increased swimming in FST
- Decreased sucrose preference indicating anhedonia
- Immediate reversal by a single dose of SSRI
- Enhanced social play
Correct Answer: Decreased sucrose preference indicating anhedonia
Q12. Which animal species is increasingly used for high-throughput behavioral screening of CNS-active compounds and allows genetic manipulation?
- Guinea pig
- Zebrafish
- Dog
- Sheep
Correct Answer: Zebrafish
Q13. The head-twitch response in rodents is commonly used as an indicator of activation of which receptor subtype?
- GABA-A receptor
- 5-HT2A receptor
- Dopamine D2 receptor
- NMDA receptor
Correct Answer: 5-HT2A receptor
Q14. Which of the following is a limitation of acute behavioral screens like FST and TST for antidepressant discovery?
- They reliably model chronic onset of therapeutic effects
- They cannot detect monoamine reuptake inhibitors
- They favor compounds with acute stimulant properties
- They are specific for non-monoaminergic drugs
Correct Answer: They favor compounds with acute stimulant properties
Q15. Which biochemical assay directly assesses inhibition of serotonin reuptake in vitro?
- Monoamine oxidase activity assay
- Serotonin transporter uptake assay
- GABA concentration by HPLC
- c-Fos immunohistochemistry
Correct Answer: Serotonin transporter uptake assay
Q16. When validating a new screening model, demonstrating that clinically effective antidepressants reverse model deficits establishes which validity?
- Face validity
- Construct validity
- Predictive validity
- Internal validity
Correct Answer: Predictive validity
Q17. Which parameter is crucial to control to avoid strain-dependent variability in antidepressant screening studies?
- Lighting only during tests
- Animal strain and housing conditions
- Brand of water bottles
- Type of bedding exclusively
Correct Answer: Animal strain and housing conditions
Q18. Which neurotransmitter hypothesis is most directly evaluated by the reserpine reversal and uptake inhibition assays?
- Glutamate hypothesis
- Monoamine hypothesis
- Neuroinflammation hypothesis
- Neurotrophic hypothesis
Correct Answer: Monoamine hypothesis
Q19. In behavioral pharmacology, why is it important to include locomotor activity controls when assessing antidepressant-like effects?
- To measure sedation only
- To distinguish psychostimulant effects from true antidepressant-like effects
- To measure food intake changes
- Locomotor activity is irrelevant to antidepressant screening
Correct Answer: To distinguish psychostimulant effects from true antidepressant-like effects
Q20. Which chronic model is used to produce hippocampal atrophy and cognitive changes relevant to depression studies?
- Acute tail suspension
- Chronic unpredictable mild stress (CMS)
- Single forced swim session
- Immediate reserpine administration
Correct Answer: Chronic unpredictable mild stress (CMS)
Q21. Which assay provides direct evidence of receptor occupancy by a drug in brain tissue?
- Behavioral despair tests
- Receptor binding autoradiography
- Open field test
- Forced swim test
Correct Answer: Receptor binding autoradiography
Q22. Sucrose preference reduction in rodents after chronic stress is primarily interpreted as a sign of:
- Anxiolytic-like effect
- Anhedonia
- Hyperactivity
- Improved cognition
Correct Answer: Anhedonia
Q23. Which of the following is an ethical consideration specific to animal screening models for CNS drugs?
- Ensuring blinding of outcome assessors only
- Minimizing unnecessary suffering and using humane endpoints
- Using only male animals without justification
- Excluding pharmacokinetic assessments
Correct Answer: Minimizing unnecessary suffering and using humane endpoints
Q24. Microdialysis combined with HPLC in antidepressant screening is primarily used to measure:
- Gene expression changes
- Extracellular monoamine concentrations
- Whole-brain electrical activity
- Protein-protein interactions
Correct Answer: Extracellular monoamine concentrations
Q25. Which model is particularly useful for evaluating antidepressant effects that require chronic administration and neuroplastic changes?
- Single-session FST
- Chronic unpredictable mild stress
- One-time tail suspension
- Acute locomotor test
Correct Answer: Chronic unpredictable mild stress
Q26. High-throughput in vitro screening for antidepressant leads often includes assays targeting which protein?
- Acetylcholinesterase
- Serotonin transporter (SERT)
- RNA polymerase
- Albumin binding
Correct Answer: Serotonin transporter (SERT)
Q27. Which outcome would suggest that a tested compound has non-specific stimulant effects rather than true antidepressant-like action?
- Reduced immobility in FST accompanied by increased open-field locomotion
- Reversal of anhedonia in sucrose test with no locomotor change
- Normalization of sleep architecture with chronic dosing
- Specific receptor occupancy correlated with behavioral change
Correct Answer: Reduced immobility in FST accompanied by increased open-field locomotion
Q28. Which test can detect prolonged antidepressant-like effects after chronic treatment and models behavioral despair extinction?
- Repeated forced swim sessions with chronic dosing
- Single acute tail suspension only
- One-time sucrose preference test
- Immediate reserpine injection
Correct Answer: Repeated forced swim sessions with chronic dosing
Q29. Which biomarker change is often associated with chronic antidepressant treatment and is measurable in screening studies?
- Decreased BDNF expression in hippocampus
- Increased hippocampal BDNF expression
- Total loss of monoamines
- Immediate increase in GFAP consistent with neurodegeneration
Correct Answer: Increased hippocampal BDNF expression
Q30. In translational screening, combining behavioral assays with which other approach improves confidence in antidepressant potential?
- Single-animal anecdotes
- Complementary biochemical, pharmacokinetic and receptor occupancy studies
- Skipping dose–response studies
- Using only one acute behavioral test
Correct Answer: Complementary biochemical, pharmacokinetic and receptor occupancy studies
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