Screening models for CNS activity are essential for evaluating candidate drugs targeting anti-parkinsonism and Alzheimer’s disease. This concise introduction for B. Pharm students covers in vivo and in vitro screening models, behavioral assays, biochemical and histological endpoints, and translational considerations. Key keywords include 6‑OHDA, MPTP, rotenone, scopolamine, APP/PS1, Morris water maze, Y‑maze, rotarod, cholinesterase inhibition, dopamine, amyloid‑beta, tau, neuroprotection, and oxidative stress. Understanding model selection, strengths, limitations, and common assays (AChE, TH immunostaining, cell viability, PET imaging) helps design robust preclinical studies and interpret pharmacological outcomes. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which neurotoxin is most commonly used to create a unilateral nigrostriatal lesion in rats to model Parkinson’s disease?
- 6‑Hydroxydopamine (6‑OHDA)
- MPTP
- Scopolamine
- Streptozotocin (ICV)
Correct Answer: 6‑Hydroxydopamine (6‑OHDA)
Q2. Which compound is used to induce Parkinsonian features in mice by targeting dopaminergic neurons after systemic administration?
- Scopolamine
- MPTP
- APP/PS1 transgene
- Rotenone
Correct Answer: MPTP
Q3. Which behavioral test assesses bradykinesia and coordination in rodent models of Parkinson’s disease?
- Morris water maze
- Y‑maze spontaneous alternation
- Pole test
- Passive avoidance
Correct Answer: Pole test
Q4. Which in vitro cell line is commonly used for screening neuroprotective effects relevant to dopaminergic neurons?
- SH‑SY5Y
- HEK293
- NIH‑3T3
- C2C12
Correct Answer: SH‑SY5Y
Q5. Scopolamine is primarily used in preclinical models to induce deficits relevant to which disease?
- Parkinson’s disease
- Huntington’s disease
- Alzheimer’s disease (memory impairment)
- Multiple sclerosis
Correct Answer: Alzheimer’s disease (memory impairment)
Q6. Which transgenic mouse model overexpresses human amyloid precursor protein and is widely used to study amyloid pathology?
- Tg2576
- 6‑OHDA rat
- Tau P301L only
- MPTP mouse
Correct Answer: Tg2576
Q7. Which behavioral test is most appropriate to evaluate spatial learning and memory in Alzheimer’s disease models?
- Rotarod
- Morris water maze
- Pole test
- Open field grooming
Correct Answer: Morris water maze
Q8. Which biochemical assay is commonly used to screen for cholinesterase inhibitory activity relevant to AD symptomatic therapy?
- Thiobarbituric acid reactive substances (TBARS)
- AChE activity assay
- Tyrosine hydroxylase (TH) assay
- DAT binding assay
Correct Answer: AChE activity assay
Q9. Which toxin model mimics environmental pesticide exposure leading to Parkinsonian pathology via mitochondrial complex I inhibition?
- Scopolamine
- Reserpine
- Rotenone
- Streptozotocin (ICV)
Correct Answer: Rotenone
Q10. In Parkinson’s screening, loss of which marker in the substantia nigra is a standard histological endpoint?
- Acetylcholinesterase (AChE)
- Tyrosine hydroxylase (TH)
- Choline acetyltransferase (ChAT)
- GFAP
Correct Answer: Tyrosine hydroxylase (TH)
Q11. Which behavioral paradigm measures recognition memory commonly used in AD preclinical studies?
- Novel object recognition
- Forced swim test
- Grip strength
- Rotarod endurance
Correct Answer: Novel object recognition
Q12. Streptozotocin administered intracerebroventricularly (ICV) is used to model which AD‑related feature?
- Parkinsonian tremor
- Insulin signaling impairment and cognitive deficits
- Alpha‑synuclein aggregation
- Peripheral neuropathy
Correct Answer: Insulin signaling impairment and cognitive deficits
Q13. Which assay is useful for assessing cell viability in neurotoxicity and neuroprotection screening?
- MTT assay
- ELISA for cytokines only
- Western blot for actin only
- Patch‑clamp exclusively
Correct Answer: MTT assay
Q14. Which experimental model is commonly used to study tau pathology relevant to Alzheimer’s disease?
- 3xTg‑AD and P301L tau transgenic mice
- 6‑OHDA rat only
- MPTP mouse
- Scopolamine acute model
Correct Answer: 3xTg‑AD and P301L tau transgenic mice
Q15. Haloperidol‑induced catalepsy in rodents is most often used to screen drugs with which potential effect?
- Cognitive enhancers for AD
- Anti‑parkinsonian dopaminergic agonist activity
- Antidepressant activity
- Anticonvulsant efficacy
Correct Answer: Anti‑parkinsonian dopaminergic agonist activity
Q16. Which imaging modality and ligand are commonly used preclinically to assess presynaptic dopaminergic terminals?
- PET with DAT ligands
- MRI with gadolinium for synapses
- Ultrasound for dopamine
- CT scan with iodinated contrast
Correct Answer: PET with DAT ligands
Q17. Which outcome would indicate neuroprotective efficacy in a PD model after drug treatment?
- Increased AChE activity in hippocampus
- Preservation of TH‑positive neurons in substantia nigra
- Increased amyloid plaques
- Reduced blood glucose only
Correct Answer: Preservation of TH‑positive neurons in substantia nigra
Q18. For AD symptomatic screening, which mechanism of action is validated clinically and commonly screened for preclinically?
- Cholinesterase inhibition
- MAO‑B activation
- NMDA receptor agonism
- Dopamine D2 antagonism
Correct Answer: Cholinesterase inhibition
Q19. Which endpoint assesses oxidative stress in brain tissue after neurotoxic insult?
- Measurement of TBARS or MDA levels
- Rotarod latency only
- DAT binding exclusively
- Serum creatinine
Correct Answer: Measurement of TBARS or MDA levels
Q20. Which in vitro model allows study of alpha‑synuclein aggregation relevant to Parkinson’s pathology?
- Primary mesencephalic cultures or SH‑SY5Y with alpha‑syn overexpression
- Hepatocyte cultures
- Cardiomyocyte primary culture
- Fibroblast cultures only
Correct Answer: Primary mesencephalic cultures or SH‑SY5Y with alpha‑syn overexpression
Q21. Which lesion model involves direct injection of excitotoxic agent into the hippocampus to study memory circuits?
- Ibotenic acid lesion
- 6‑OHDA nigral lesion
- MPTP systemic injection
- Rotenone chronic infusion
Correct Answer: Ibotenic acid lesion
Q22. Which parameter in the open field test is commonly interpreted as a measure of general locomotor activity?
- Time to find hidden platform
- Total distance traveled
- Latency to fall
- Spontaneous alternation percentage
Correct Answer: Total distance traveled
Q23. Which biomarker is directly associated with synaptic integrity and is measured in AD studies?
- Synaptophysin
- Myelin basic protein
- Albumin
- Creatine kinase
Correct Answer: Synaptophysin
Q24. In pharmacological screening, which effect of MAO‑B inhibitors is particularly relevant for Parkinson’s disease?
- Enhance cholinergic transmission
- Reduce dopamine breakdown and increase synaptic dopamine
- Increase amyloid aggregation
- Block NMDA receptors
Correct Answer: Reduce dopamine breakdown and increase synaptic dopamine
Q25. Which preclinical consideration is critical when extrapolating neuroprotective findings to clinical trials?
- Species differences and dosing regimens
- Only using in vitro data without in vivo follow up
- Ignoring behavioral outcomes
- Relying solely on peripheral biomarkers
Correct Answer: Species differences and dosing regimens
Q26. The Y‑maze spontaneous alternation test primarily evaluates which cognitive domain?
- Motor coordination
- Working memory and spatial recognition
- Depressive‑like behavior
- Nociceptive threshold
Correct Answer: Working memory and spatial recognition
Q27. Which effect would indicate a successful anti‑parkinsonian symptomatic drug in rotarod testing?
- Decreased latency to fall
- Increased latency to fall (improved motor performance)
- Increased immobility only
- Reduced exploratory sniffing
Correct Answer: Increased latency to fall (improved motor performance)
Q28. Intracerebral infusion of aggregated amyloid‑beta peptides in rodents is used to model which feature?
- Motor neuron degeneration only
- Acute cholinergic hyperactivity
- Localized amyloid toxicity and memory impairment
- Peripheral inflammation
Correct Answer: Localized amyloid toxicity and memory impairment
Q29. Which post‑mortem assay is used to quantify amyloid plaques in brain tissue?
- Thioflavin S or Congo red staining
- HPLC for neurotransmitters only
- ELISA for insulin exclusively
- Western blot for myosin
Correct Answer: Thioflavin S or Congo red staining
Q30. Which limitation is most associated with toxin‑based PD models compared with genetic models?
- Toxin models always reproduce progressive Lewy body pathology
- Toxin models often lack chronic progressive pathology and genetic complexity of human PD
- Toxin models are identical to human sporadic PD
- Toxin models do not require ethical approval
Correct Answer: Toxin models often lack chronic progressive pathology and genetic complexity of human PD

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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