Screening models for CNS activity – antipyretics introduce B.Pharm students to essential preclinical assays used to evaluate central nervous system effects and fever-reducing potential of new molecules. This concise guide covers behavioral and physiological models—such as hot plate, tail‑flick, open field, rotarod, elevated plus maze, forced swim, PTZ and MES—and antipyretic assays like brewer’s yeast, LPS and prostaglandin E2-induced fever. Key concepts include endpoints, species selection, dose-response, mechanism probing (COX inhibition, PGE2, neurotransmitter changes), and limitations of each model. Mastery of these screening tools helps bridge pharmacology, formulation and safety evaluation. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which model primarily assesses supraspinal analgesic activity in rodents?
- Tail‑flick test
- Hot plate test
- Formalin test
- Acetic acid writhing test
Correct Answer: Hot plate test
Q2. The tail‑flick test is most sensitive to analgesics acting via which mechanism?
- Peripheral prostaglandin inhibition
- Spinal reflex modulation
- Supraspinal opioid pathways
- Anti‑inflammatory cytokine reduction
Correct Answer: Spinal reflex modulation
Q3. Which assay is commonly used to screen anticonvulsant efficacy against generalized tonic‑clonic seizures?
- Pentylenetetrazole (PTZ) test
- Maximal electroshock seizure (MES) test
- Rotarod test
- Open field test
Correct Answer: Maximal electroshock seizure (MES) test
Q4. Pentylenetetrazole (PTZ) induced seizure model is primarily used to detect drugs effective against:
- Generalized tonic‑clonic seizures
- Absence and myoclonic seizures
- Status epilepticus only
- Focal seizures exclusively
Correct Answer: Absence and myoclonic seizures
Q5. Which behavioral test is most appropriate for initial screening of anxiolytic activity?
- Forced swim test
- Elevated plus maze
- Hot plate test
- Morris water maze
Correct Answer: Elevated plus maze
Q6. Increased open arm entries in the elevated plus maze indicate:
- Increased anxiety
- Decreased locomotion
- Anxiolytic effect
- Impaired coordination
Correct Answer: Anxiolytic effect
Q7. The forced swim test (FST) is used to screen for potential:
- Analgesics
- Antidepressants
- Antipyretics
- Anticonvulsants
Correct Answer: Antidepressants
Q8. In the forced swim test, a decrease in immobility time typically suggests:
- Pro‑depressive effect
- Antidepressant‑like effect
- Neurotoxic damage
- Impaired thermoregulation
Correct Answer: Antidepressant‑like effect
Q9. Which model assesses motor coordination and balance in rodents for neurotoxicity or sedative side effects?
- Open field test
- Rotarod test
- Tail‑suspension test
- Hot plate test
Correct Answer: Rotarod test
Q10. A drug that decreases total distance traveled in the open field test is likely to have which effect?
- Stimulant effect
- Sedative or locomotor depressant effect
- Anxiolytic effect increasing exploration
- Enhanced learning and memory
Correct Answer: Sedative or locomotor depressant effect
Q11. The Morris water maze is primarily used to evaluate:
- Analgesic potency
- Spatial learning and memory
- Pyrexia response
- Motor coordination
Correct Answer: Spatial learning and memory
Q12. Which biochemical marker is often measured to support antipyretic activity of a test compound?
- Glutamate levels in hippocampus
- Prostaglandin E2 (PGE2) levels
- Acetylcholinesterase activity
- Serotonin turnover
Correct Answer: Prostaglandin E2 (PGE2) levels
Q13. Which animal model is most widely used for primary screening of antipyretic activity?
- Brewer’s yeast‑induced pyrexia
- Hot plate test
- Rotarod test
- Pain threshold tail‑flick
Correct Answer: Brewer’s yeast‑induced pyrexia
Q14. Lipopolysaccharide (LPS) induced fever model is useful for evaluating antipyretics acting via:
- Peripheral COX inhibition only
- Immune‑mediated cytokine pathways and central PGE2 signaling
- Direct opioid receptor activation
- Ion channel blockade in peripheral nerves
Correct Answer: Immune‑mediated cytokine pathways and central PGE2 signaling
Q15. In yeast‑induced fever model, what is the common readout to assess antipyretic effect?
- Serum glucose change
- Reduction in rectal temperature compared to control
- Duration of sleep
- Open arm entries in elevated plus maze
Correct Answer: Reduction in rectal temperature compared to control
Q16. Which mechanism is central to classical antipyretic action of NSAIDs?
- Inhibition of monoamine oxidase
- Inhibition of COX enzymes decreasing PGE2 synthesis
- Blockade of NMDA receptors
- Activation of GABAergic neurotransmission
Correct Answer: Inhibition of COX enzymes decreasing PGE2 synthesis
Q17. The formalin test’s biphasic pain response allows screening for both:
- Only central analgesic effects
- Antipyretic and anticonvulsant effects
- Peripheral inflammatory and central sensitization analgesic effects
- Motor coordination deficits and sedation
Correct Answer: Peripheral inflammatory and central sensitization analgesic effects
Q18. Which of the following is a limitation when using rodent models to predict human CNS responses?
- Perfect translation to human pharmacokinetics
- Identical receptor distribution across species
- Differences in metabolism, receptor expression and behavioral readouts
- No ethical considerations
Correct Answer: Differences in metabolism, receptor expression and behavioral readouts
Q19. Measurement of brain-to-plasma concentration ratio primarily informs about a compound’s:
- Renal clearance
- Blood–brain barrier penetration
- Antipyretic potency in vivo
- CYP450 induction potential
Correct Answer: Blood–brain barrier penetration
Q20. Which in vivo test helps differentiate sedative from motor‑impairing effects?
- Hot plate test
- Rotarod performance combined with open field locomotion
- Brewer’s yeast fever assay
- Pentylenetetrazole challenge only
Correct Answer: Rotarod performance combined with open field locomotion
Q21. For antipyretic screening, prostaglandin E2 (PGE2)‑induced fever model is specifically used to:
- Assess direct action on hypothalamic set point via PGE2 pathways
- Evaluate peripheral nociceptive thresholds
- Measure locomotor activity changes
- Test anticonvulsant efficacy
Correct Answer: Assess direct action on hypothalamic set point via PGE2 pathways
Q22. Which parameter is critical when designing behavioral CNS studies to reduce variability?
- Using mixed‑species groups
- Standardizing animal age, sex, time of day and environment
- Avoiding control groups altogether
- Changing protocols mid‑experiment for adaptability
Correct Answer: Standardizing animal age, sex, time of day and environment
Q23. A test compound that shortens pentobarbital‑induced sleep time likely has what property?
- Sedative‑hypnotic potency
- Stimulant or central nervous system activating property
- Antipyretic activity via COX inhibition
- Pure peripheral analgesic action only
Correct Answer: Stimulant or central nervous system activating property
Q24. Which statistical consideration is particularly important in preclinical screening to establish validity?
- Using single animal per group is sufficient
- Appropriate sample size, randomization and blinding
- Reporting only positive outcomes
- Changing endpoints after seeing data
Correct Answer: Appropriate sample size, randomization and blinding
Q25. Which in vitro assay can be used early to predict CNS receptor binding before in vivo screening?
- Radioligand binding assay using target receptor homogenate
- Yeast fever induction
- Hot plate latency measurement
- Rotarod test on cultured cells
Correct Answer: Radioligand binding assay using target receptor homogenate
Q26. NSAID efficacy in fever models correlates best with their ability to reduce:
- Hypothalamic PGE2 synthesis
- Serotonin reuptake
- Dopamine release in striatum
- Acetylcholine levels in cortex
Correct Answer: Hypothalamic PGE2 synthesis
Q27. Which model is most suitable to evaluate antidepressant effect related to behavioral despair?
- Rotarod test
- Forced swim test and tail suspension test
- Brewer’s yeast fever test
- Maximal electroshock seizure test
Correct Answer: Forced swim test and tail suspension test
Q28. An ideal preclinical screening cascade for a CNS drug candidate should include:
- Only in vitro tests
- In vitro receptor profiling, ADME, BBB assessment, and targeted in vivo behavioral/physiological models
- No pharmacokinetic evaluation
- Only one in vivo behavioral test
Correct Answer: In vitro receptor profiling, ADME, BBB assessment, and targeted in vivo behavioral/physiological models
Q29. During yeast‑induced fever assay, which control is essential to validate antipyretic effect?
- Untreated fevered group and vehicle control group
- Only drug treated animals without fever induction
- Using only in vitro temperature measurements
- Replacement of rectal measurements with ambient temperature
Correct Answer: Untreated fevered group and vehicle control group
Q30. Which ethical practice is mandatory when performing animal screening for CNS and antipyretic activity?
- Ignoring humane endpoints to gather more data
- Approval from Institutional Animal Ethics Committee and adherence to 3Rs (Replacement, Reduction, Refinement)
- No reporting of welfare measures
- Using excess animal numbers without justification
Correct Answer: Approval from Institutional Animal Ethics Committee and adherence to 3Rs (Replacement, Reduction, Refinement)
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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