Screening models for antiepileptic and nootropic agents MCQs With Answer

Introduction: This quiz collection is designed for M.Pharm students studying Pharmacological and Toxicological Screening Methods-I, focusing on screening models for antiepileptic and nootropic agents. The questions cover in vivo and in vitro seizure models (MES, PTZ, kindling, kainic acid/pilocarpine, 6‑Hz, audiogenic, zebrafish), behavioral paradigms for cognitive assessment (Morris water maze, passive avoidance, object recognition, Y‑maze, radial arm maze), biochemical markers (AChE, BDNF), and key pharmacological endpoints (ED50, protective index, antiepileptogenic evaluation). These MCQs emphasize mechanism, endpoints, strengths and limitations of models to help you apply screening concepts in experimental design and data interpretation.

Q1. Which characteristic response in the maximal electroshock seizure (MES) model is most predictive of an agent’s efficacy against generalized tonic–clonic seizures?

• Protection against tonic hindlimb extension
• Suppression of brief clonic facial jerks
• Reduction in absence-like spike‑and‑wave discharges
• Prevention of focal limbic seizures only

Correct Answer: Protection against tonic hindlimb extension

Q2. The pentylenetetrazol (PTZ) chemical seizure model is primarily used to identify compounds effective against which seizure types and via what principal mechanism?

• Generalized tonic–clonic seizures through sodium channel blockade
• Absence and myoclonic seizures via GABA-A receptor antagonism reversal
• Focal temporal lobe seizures by NMDA receptor antagonism
• Acoustic seizures in DBA/2 mice by modulation of glycine receptors

Correct Answer: Absence and myoclonic seizures via GABA-A receptor antagonism reversal

Q3. Kindling models are especially valuable because they model which clinically relevant process?

• Acute seizure threshold elevation following single high‑dose stimulation
• Progressive development of permanent hyperexcitability and epileptogenesis after repeated subconvulsive stimuli
• Immediate status epilepticus induction without chronic sequelae
• Purely genetic absence epilepsy without environmental influence

Correct Answer: Progressive development of permanent hyperexcitability and epileptogenesis after repeated subconvulsive stimuli

Q4. The 6‑Hz psychomotor seizure model is particularly useful in preclinical screening because it:

• Models absence seizures seen in children
• Is sensitive to drugs effective against pharmacoresistant partial seizures
• Requires intracerebral kainic acid administration for induction
• Is primarily a screen for muscle relaxant properties

Correct Answer: Is sensitive to drugs effective against pharmacoresistant partial seizures

Q5. Which statement correctly distinguishes kainic acid and pilocarpine models used to generate status epilepticus and chronic epilepsy?

• Kainic acid is a muscarinic agonist; pilocarpine is a kainate receptor agonist
• Pilocarpine activates muscarinic receptors; kainic acid is a glutamate (kainate) receptor agonist
• Both act primarily via GABA-A receptor antagonism
• Neither produces neuronal loss or spontaneous recurrent seizures

Correct Answer: Pilocarpine activates muscarinic receptors; kainic acid is a glutamate (kainate) receptor agonist

Q6. Audiogenic seizure models are commonly used with which rodent strain that shows innate sound‑induced seizures?

• Wistar rats
• Sprague–Dawley rats
• DBA/2 mice
• C57BL/6 mice

Correct Answer: DBA/2 mice

Q7. One major advantage of using zebrafish larvae for antiepileptic drug screening is:

• Their brain anatomy is identical to rodents
• They permit high‑throughput, whole‑organism phenotypic screening with optical readouts
• They only respond to GABAergic drugs, simplifying interpretation
• They require intracranial electrode implantation for all assays

Correct Answer: They permit high‑throughput, whole‑organism phenotypic screening with optical readouts

Q8. Which behavioral model is most widely used to assess spatial learning and long‑term reference memory in rodents for nootropic screening?

• Open field test
• Morris water maze
• Grip strength assay
• Forced swim test

Correct Answer: Morris water maze

Q9. Which pharmacological model is commonly used to induce reversible amnesia in rodents for testing memory‑enhancing agents?

• Pilocarpine‑induced status epilepticus
• Scopolamine‑induced amnesia
• PTZ‑induced convulsions
• 6‑Hz seizure induction

Correct Answer: Scopolamine‑induced amnesia

Q10. The novel object recognition test primarily measures which form of memory relevant to nootropic screening?

• Working memory for procedural tasks
• Recognition memory and short‑term declarative memory
• Acoustic startle habituation
• Motor learning on the rotarod

Correct Answer: Recognition memory and short‑term declarative memory

Q11. Which colorimetric assay is the standard method for measuring acetylcholinesterase activity in brain homogenates during nootropic evaluation?

• Bradford protein assay
• Ellman’s method (DTNB assay)
• Western blotting for AChE protein
• ELISA for acetylcholine

Correct Answer: Ellman’s method (DTNB assay)

Q12. In anticonvulsant screening, the protective index (PI) is defined as which ratio?

• ED50/TD50 (median effective dose divided by median toxic dose)
• TD50/ED50 (median toxic dose divided by median effective dose)
• LD50 × ED50
• ED90/ED10

Correct Answer: TD50/ED50 (median toxic dose divided by median effective dose)

Q13. In the MES test the ED50 for a candidate antiepileptic is defined as the dose that:

• Kills 50% of the animals
• Produces seizures in 50% of animals
• Protects 50% of animals from tonic hindlimb extension
• Causes sedation in 50% of animals

Correct Answer: Protects 50% of animals from tonic hindlimb extension

Q14. A frequently used electrophysiological marker of kindling progression is:

• Increase in hippocampal gamma oscillation power only
• Progressive increase in afterdischarge duration and lowering of afterdischarge threshold
• Immediate neuroprotection against excitotoxic injury
• Absence of behavioral seizures despite electrical stimulation

Correct Answer: Progressive increase in afterdischarge duration and lowering of afterdischarge threshold

Q15. To detect motor side effects or sedation induced by a nootropic or anticonvulsant compound, which behavioral test is most appropriate?

• Morris water maze
• Rotarod performance test
• Novel object recognition
• Passive avoidance step‑through

Correct Answer: Rotarod performance test

Q16. Which neurochemical biomarker measured in hippocampus is often used to indicate neurotrophic effects of putative nootropics?

• Plasma glucose concentration
• Hippocampal brain‑derived neurotrophic factor (BDNF) levels
• Cerebral sodium channel expression only
• Hepatic cytochrome P450 content

Correct Answer: Hippocampal brain‑derived neurotrophic factor (BDNF) levels

Q17. Spontaneous alternation in the Y‑maze is primarily used to assess which cognitive domain?

• Spatial working memory
• Long‑term reference memory
• Fear‑conditioned freezing
• Olfactory discrimination

Correct Answer: Spatial working memory

Q18. Which pharmacological challenge is often used as a negative control to induce transient memory impairment for validation of nootropic effects?

• Low‑dose kainic acid causing status epilepticus
• Diazepam‑induced amnesia
• PTZ‑induced generalized seizures
• Six‑Hz electroshock protection

Correct Answer: Diazepam‑induced amnesia

Q19. In the PTZ seizure model, a commonly used endpoint indicating anticonvulsant activity is:

• Decrease in the latency to first clonic seizure
• Increase in latency to first myoclonic or clonic seizure and/or increase in seizure threshold
• Occurrence of spontaneous recurrent seizures without challenge
• Only changes in heart rate

Correct Answer: Increase in latency to first myoclonic or clonic seizure and/or increase in seizure threshold

Q20. Which preclinical model is most commonly used to evaluate antiepileptogenic (disease‑modifying) potential rather than acute anticonvulsant activity?

• Single‑shock MES assay
• Acute PTZ seizure test
• Kindling model with repeated subthreshold stimulation
• Rotarod motor coordination test

Correct Answer: Kindling model with repeated subthreshold stimulation

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