Screening models for CNS activity – analgesics MCQs With Answer

Screening models for CNS activity – analgesics MCQs With Answer

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Introduction
Screening models for CNS activity are essential in evaluating analgesics during preclinical development. B. Pharm students must grasp common screening assays — tail-flick, hot-plate, formalin, writhing, and neuropathic models — plus endpoints like antinociceptive latency, ED50, therapeutic index, and behavioral confounds. Understanding mechanisms (opioid mu receptors, COX inhibition, NMDA modulation, alpha2-delta calcium channels), dose-response relationships, and assay limitations improves interpretation of efficacy, toxicity, and translational relevance. Familiarity with controls, blinding, and motor coordination tests (rotarod) is crucial to avoid false positives. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary purpose of screening models for CNS activity in analgesic research?

  • To evaluate antinociceptive efficacy and dose–response of candidate analgesics
  • To determine commercial pricing for new drugs
  • To replace clinical trials entirely
  • To measure only drug metabolism rates

Correct Answer: To evaluate antinociceptive efficacy and dose–response of candidate analgesics

Q2. Which preclinical test primarily measures spinal reflex nociceptive responses?

  • Hot plate test
  • Formalin test
  • Tail-flick (tail immersion) test
  • Writhing (acetic acid) test

Correct Answer: Tail-flick (tail immersion) test

Q3. Which assay is most sensitive to supraspinal (brain-mediated) analgesic effects?

  • Tail-flick test
  • Hot plate test
  • Rotarod test
  • Open field locomotion

Correct Answer: Hot plate test

Q4. The formalin test shows a biphasic pain response; what do the two phases represent?

  • Phase 1 = inflammatory, Phase 2 = neurogenic
  • Phase 1 = neuropathic, Phase 2 = visceral
  • Phase 1 = neurogenic (acute), Phase 2 = inflammatory (tonic)
  • Phase 1 = motor impairment, Phase 2 = sedation

Correct Answer: Phase 1 = neurogenic (acute), Phase 2 = inflammatory (tonic)

Q5. Which test is most commonly used to screen peripheral analgesic activity mediated by prostaglandin pathways?

  • Hot plate test
  • Tail-flick test
  • Writhing (acetic acid) test
  • Rotarod test

Correct Answer: Writhing (acetic acid) test

Q6. Which behavioural assay is used to detect motor impairment that can confound analgesic screening?

  • Formalin test
  • Rotarod test
  • Hot plate test
  • Tail flick test

Correct Answer: Rotarod test

Q7. Which antagonist is most commonly used to demonstrate opioid-mediated analgesia reversal in screening models?

  • Atropine
  • Naloxone
  • Propranolol
  • Flumazenil

Correct Answer: Naloxone

Q8. Which opioid receptor subtype is primarily responsible for classical analgesia in many screening tests?

  • Kappa (κ) receptor only
  • Delta (δ) receptor only
  • Mu (µ) receptor
  • Sigma receptor

Correct Answer: Mu (µ) receptor

Q9. What is the primary mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) in analgesia models?

  • Blocking sodium channels in axons
  • Inhibiting cyclooxygenase (COX) enzymes to reduce prostaglandin synthesis
  • Agonizing µ-opioid receptors
  • Enhancing GABAergic inhibition

Correct Answer: Inhibiting cyclooxygenase (COX) enzymes to reduce prostaglandin synthesis

Q10. A compound shows analgesic activity in the hot plate test but not in the tail-flick test. What is the most likely interpretation?

  • It primarily has peripheral anti-inflammatory action
  • It is likely sedative without analgesic effect
  • It may act predominantly at supraspinal sites
  • It is ineffective and results are false positives

Correct Answer: It may act predominantly at supraspinal sites

Q11. How is ED50 defined in the context of analgesic screening?

  • The dose producing toxicity in 50% of animals
  • The dose producing 50% of the maximal pharmacological effect
  • The concentration that inhibits 50% of a biochemical reaction in vitro
  • The dose that kills 50% of a population

Correct Answer: The dose producing 50% of the maximal pharmacological effect

Q12. Therapeutic index is commonly calculated as which ratio?

  • ED50 / TD50
  • TD50 / ED50
  • LD50 × ED50
  • IC50 / EC50

Correct Answer: TD50 / ED50

Q13. Which phase of the formalin test is most sensitive to anti-inflammatory agents?

  • Phase 1 (0–5 min)
  • Phase 2 (15–60 min)
  • Both phases equally
  • Neither phase

Correct Answer: Phase 2 (15–60 min)

Q14. In the tail-flick assay the primary measured endpoint is:

  • Number of writhes per minute
  • Latency to tail withdrawal from a heat stimulus
  • Time spent on a rotating rod
  • Paw licking duration

Correct Answer: Latency to tail withdrawal from a heat stimulus

Q15. In the hot plate test, which behavioral responses are typically recorded as analgesic endpoints?

  • Paw licking or jumping latency
  • Number of grooming episodes
  • Body temperature changes
  • Feeding behavior

Correct Answer: Paw licking or jumping latency

Q16. Which animal model is commonly used to study neuropathic pain mechanisms in analgesic screening?

  • Formalin paw injection only
  • Chronic constriction injury (CCI) of the sciatic nerve
  • Hot plate at low temperature
  • Acetic acid writhing with low dose

Correct Answer: Chronic constriction injury (CCI) of the sciatic nerve

Q17. Which test is most appropriate to detect sedative or motor side effects that could confound analgesic readouts?

  • Formalin test
  • Rotarod performance test
  • Tail-flick latency
  • Hot plate latency

Correct Answer: Rotarod performance test

Q18. Antidepressant drugs produce analgesia in some neuropathic models primarily by:

  • Blocking COX enzymes
  • Inhibiting serotonin and norepinephrine reuptake to enhance descending inhibition
  • Direct agonism at opioid receptors
  • Blocking voltage-gated sodium channels exclusively

Correct Answer: Inhibiting serotonin and norepinephrine reuptake to enhance descending inhibition

Q19. Gabapentinoids (gabapentin, pregabalin) exert analgesic effects mainly by binding to:

  • Mu-opioid receptors
  • NMDA receptor glycine site
  • Alpha2-delta subunit of voltage-gated calcium channels
  • Serotonin receptors

Correct Answer: Alpha2-delta subunit of voltage-gated calcium channels

Q20. NMDA receptor antagonists are useful in analgesic screening because they:

  • Reduce peripheral prostaglandin synthesis
  • Directly activate opioid receptors
  • Attenuate central sensitization and hyperalgesia
  • Increase acetylcholine release

Correct Answer: Attenuate central sensitization and hyperalgesia

Q21. In pharmacology, the term ‘potency’ refers to:

  • The maximum effect a drug can produce
  • The dose required to produce a defined effect relative to other drugs
  • The time to onset of action
  • The toxicity profile of a drug

Correct Answer: The dose required to produce a defined effect relative to other drugs

Q22. A competitive antagonist in a dose–response assay typically causes which change?

  • Decrease in maximal effect (Emax) only
  • Parallel rightward shift of the dose–response curve with no change in Emax
  • Leftward shift with increased potency
  • Complete loss of any response at all doses

Correct Answer: Parallel rightward shift of the dose–response curve with no change in Emax

Q23. A key cellular mechanism contributing to opioid tolerance in chronic screening studies is:

  • Increased prostaglandin synthesis
  • Receptor desensitization and internalization
  • Enhanced COX-2 expression only in liver
  • Permanent nerve regeneration

Correct Answer: Receptor desensitization and internalization

Q24. Which class of analgesics primarily exerts effects at peripheral nociceptors rather than centrally?

  • Opioids
  • NSAIDs (nonsteroidal anti-inflammatory drugs)
  • NMDA antagonists
  • Gabapentinoids

Correct Answer: NSAIDs (nonsteroidal anti-inflammatory drugs)

Q25. Which preclinical test is most commonly used to model visceral pain?

  • Hot plate test
  • Tail-flick test
  • Acetic acid-induced writhing test
  • Rotarod

Correct Answer: Acetic acid-induced writhing test

Q26. The biphasic nature of the formalin test makes it valuable because it:

  • Only measures motor effects
  • Separates acute neurogenic pain from persistent inflammatory pain phases
  • Measures biochemical enzyme levels directly
  • Is insensitive to opioids

Correct Answer: Separates acute neurogenic pain from persistent inflammatory pain phases

Q27. IC50 commonly refers to:

  • The dose that produces 50% of an in vivo analgesic effect
  • The concentration of an inhibitor that reduces a biological process by 50% in vitro
  • The lethal dose for 50% of animals
  • The time to 50% recovery

Correct Answer: The concentration of an inhibitor that reduces a biological process by 50% in vitro

Q28. Why are appropriate vehicle controls and blinding important in analgesic screening?

  • They increase animal discomfort intentionally
  • They prevent biases and distinguish drug effects from formulation or observer bias
  • They reduce the need for statistical analysis
  • They permit higher dosing without toxicity

Correct Answer: They prevent biases and distinguish drug effects from formulation or observer bias

Q29. Which drug is commonly used as a positive control for central analgesic activity in screening models?

  • Ibuprofen
  • Morphine
  • Acetaminophen at low dose
  • Vehicle (saline)

Correct Answer: Morphine

Q30. A major limitation of animal screening models for CNS analgesics is:

  • They perfectly predict human clinical efficacy
  • High cost but no ethical concerns
  • Translational differences between animal responses and human pain experience
  • They measure only pharmacokinetics

Correct Answer: Translational differences between animal responses and human pain experience

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