Screening models for CNS activity – anti-parkinsonism and Alzheimer’s disease MCQs With Answer

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

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