Introduction
In vivo and in vitro models for CNS screening MCQs With Answer is designed for M.Pharm students preparing for advanced pharmacological and toxicological screening courses. This collection explains core assays and animal and cellular models used to evaluate CNS-active compounds, focusing on mechanisms, endpoints, strengths and limitations. Emphasis is placed on behavioral paradigms (e.g., anxiety, memory, motor function), neurodegeneration and seizure models, cell-based assays (primary neurons, immortalized lines, organotypic slices), and blood–brain barrier systems. The questions reinforce experimental design, interpretation of results, translational relevance and ethical considerations, helping students build practical knowledge for preclinical CNS drug discovery and toxicology screening.
Q1. Which in vivo model is most commonly used to mimic dopaminergic neuronal loss characteristic of Parkinson’s disease in mice?
- 6-hydroxydopamine (6-OHDA) lesion in mice
- MPTP-induced mouse model
- Kainic acid-induced seizure model
- Streptozotocin-induced diabetic model
Correct Answer: MPTP-induced mouse model
Q2. Which in vitro system best models neuronal network activity and preserves architecture comparable to in vivo brain tissue?
- Primary cortical neuron monolayer culture
- Organotypic brain slice culture
- Transwell BBB endothelial monoculture
- Immortalized HEK293 cell line
Correct Answer: Organotypic brain slice culture
Q3. Which behavioral test is commonly used to assess antidepressant-like activity by measuring behavioral despair in rodents?
- Elevated plus maze
- Forced swim test
- Rotarod test
- Morris water maze
Correct Answer: Forced swim test
Q4. For screening anticonvulsant activity, which acute seizure model involves a convulsant chemical that acts as a GABA-A receptor antagonist?
- Pentylenetetrazole (PTZ) seizure model
- Kainic acid-induced status epilepticus
- Strychnine-induced seizure model
Correct Answer: Pentylenetetrazole (PTZ) seizure model
Q5. Which immortalized human neuronal cell line is frequently used for neurotoxicity and neuroprotection assays and can be differentiated into neuron-like cells?
- BV2 microglial cell line
- PC12 (rat pheochromocytoma) cell line
- SH-SY5Y human neuroblastoma cell line
- HEK293 human embryonic kidney cell line
Correct Answer: SH-SY5Y human neuroblastoma cell line
Q6. Which assay is commonly used in vitro to measure neuronal viability based on mitochondrial metabolic activity?
- LDH release assay
- MTT (or MTS) assay
- ELISA for cytokines
- Western blot for synaptophysin
Correct Answer: MTT (or MTS) assay
Q7. In blood–brain barrier (BBB) modeling, a Transwell co-culture with endothelial cells on the insert and astrocytes beneath is primarily used to assess which parameter?
- Neuronal synaptic plasticity
- Electrical seizure threshold
- Permeability and barrier tightness (TEER)
- Microglial phagocytosis rate
Correct Answer: Permeability and barrier tightness (TEER)
Q8. Which in vivo test is most appropriate for assessing analgesic efficacy to thermal nociception in rodents?
- Tail-flick test
- Elevated plus maze
- Forced swim test
- Open field test
Correct Answer: Tail-flick test
Q9. Which neurodegeneration model uses a mitochondrial complex I inhibitor to induce dopaminergic neuron degeneration and is used as a model for Parkinson’s disease in rodents?
- 6-OHDA
- Rotenone
- Scopolamine
- PTZ
Correct Answer: Rotenone
Q10. Which electrophysiological technique is the gold standard for measuring ion channel activity at single-cell resolution in neurons?
- Electroencephalography (EEG)
- Patch-clamp recording
- Multielectrode array (MEA)
- Microdialysis
Correct Answer: Patch-clamp recording
Q11. When evaluating cognitive effects in rodents, which spatial memory test relies on the animal learning the location of a submerged platform?
- Morris water maze
- Elevated plus maze
- Hot plate test
- Y-maze spontaneous alternation
Correct Answer: Morris water maze
Q12. Organotypic hippocampal slice cultures are particularly valuable because they allow study of which of the following?
- Whole-animal pharmacokinetics
- Preserved cytoarchitecture and synaptic connectivity ex vivo
- Systemic immune responses
- Blood glucose regulation
Correct Answer: Preserved cytoarchitecture and synaptic connectivity ex vivo
Q13. Which biomarker enzyme assay is commonly used in screening for cholinesterase inhibitory activity relevant to Alzheimer’s disease?
- Monoamine oxidase (MAO) assay
- Acetylcholinesterase (AChE) inhibition assay
- Cytochrome P450 activity assay
- Lactate dehydrogenase (LDH) assay
Correct Answer: Acetylcholinesterase (AChE) inhibition assay
Q14. Which in vivo behavioral test is commonly used to evaluate anxiolytic activity by measuring open versus closed arm entries?
- Open field test
- Elevated plus maze
- Rotarod performance
- Forced swim test
Correct Answer: Elevated plus maze
Q15. In vitro blood–brain barrier permeability prediction often reports the brain-to-plasma ratio. A low ratio typically indicates what about a compound?
- High CNS penetration
- Poor CNS penetration
- High metabolic stability in brain tissue
- Ability to inhibit P-glycoprotein efflux
Correct Answer: Poor CNS penetration
Q16. Which cellular model is most suitable for studying microglial-mediated neuroinflammation in vitro?
- BV2 microglial cell line
- SH-SY5Y neuronal cell line
- HEK293 epithelial cell line
- Primary hepatocyte culture
Correct Answer: BV2 microglial cell line
Q17. The maximal electroshock (MES) test is predictive primarily of anticonvulsant efficacy against which seizure type?
- Absence seizures
- Generalized tonic-clonic seizures
- Focal seizures with retained awareness
- Non-epileptic psychogenic seizures
Correct Answer: Generalized tonic-clonic seizures
Q18. Which advantage best describes the use of human induced pluripotent stem cell (iPSC)-derived neurons for CNS screening?
- Unlimited reproducibility with identical genetics across samples
- Direct recapitulation of human-specific pathways and patient-derived genotypes
- No requirement for ethical review
- Lower cost and simplicity compared with immortalized lines
Correct Answer: Direct recapitulation of human-specific pathways and patient-derived genotypes
Q19. When validating a new in vitro neurotoxicity assay, which parameter is most important to establish predictive value for human risk?
- Inter-assay variability only
- Sensitivity, specificity and concordance with established in vivo outcomes
- Ease of automation without relevance assessment
- Low reagent cost regardless of endpoint reliability
Correct Answer: Sensitivity, specificity and concordance with established in vivo outcomes
Q20. Which ethical consideration is essential when designing in vivo CNS screening studies?
- Maximizing animal numbers to ensure statistical significance regardless of welfare
- Replacement, reduction and refinement (3Rs) to minimize animal use and suffering
- Using higher-order species as default to increase translational value
- Avoiding anesthesia to prevent confounding data
Correct Answer: Replacement, reduction and refinement (3Rs) to minimize animal use and suffering
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