Screening models for CNS activity – sedatives and hypnotics MCQs With Answer

Screening models for CNS activity are vital in B. Pharm education to evaluate sedatives and hypnotics during preclinical development. This short introduction outlines key pharmacological screening methods used to assess GABAergic agents, benzodiazepines, barbiturates and novel hypnotics. Students should learn animal behavioral assays (pentobarbital-induced sleeping time, locomotor activity, rotarod, elevated plus maze), in vitro receptor binding and chloride influx assays, and EEG-based sleep studies. Core concepts include dose–response, ED50/LD50, therapeutic index, pharmacokinetics, receptor mechanisms and use of antagonists like flumazenil to confirm activity. Familiarity with these models improves interpretation of efficacy, safety and mechanism of action. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which preclinical test is most commonly used to measure hypnotic potency by recording sleep latency and sleep duration after a standard barbiturate dose?

• Pentobarbital-induced sleeping time test
• Rotarod performance test
• Elevated plus maze
• Open-field test

Correct Answer: Pentobarbital-induced sleeping time test

Q2. Which assay directly measures binding to the benzodiazepine site on GABA-A receptors in tissue homogenates?

• Radioligand binding assay (e.g., 3H-flunitrazepam binding)
• EEG polysomnography
• Rotarod coordination test
• Pentylenetetrazol seizure threshold test

Correct Answer: Radioligand binding assay (e.g., 3H-flunitrazepam binding)

Q3. An increase in locomotor activity in the open-field test most likely indicates which type of CNS effect?

• Stimulant effect
• Hypnotic effect
• Muscle relaxation
• Anticonvulsant effect

Correct Answer: Stimulant effect

Q4. Which behavioral test is primarily used to detect motor coordination impairment caused by sedative or hypnotic drugs?

• Rotarod test
• Light–dark box
• Hole-board test
• Forced swim test

Correct Answer: Rotarod test

Q5. Which parameter represents the ratio of a drug dose causing death in 50% of animals to the dose producing the desired effect in 50% (safety margin)?

• Therapeutic index (LD50/ED50)
• Potency index (ED50/EC50)
• Safety coefficient (ED50/LD50)
• Margin of efficacy (EC50/ED50)

Correct Answer: Therapeutic index (LD50/ED50)

Q6. In pentobarbital-induced sleeping time tests, which outcome indicates that a test compound has hypnotic activity?

• Increased total sleep duration and reduced sleep latency
• Increased motor coordination time on rotarod
• Increased exploratory head-dips in hole-board
• Decreased duration of pentobarbital action

Correct Answer: Increased total sleep duration and reduced sleep latency

Q7. Which antagonist is used to reverse benzodiazepine-induced effects in receptor confirmation studies?

• Flumazenil
• Fluoxetine
• Propranolol
• Naloxone

Correct Answer: Flumazenil

Q8. Which in vitro functional assay directly assesses GABA-A receptor-mediated chloride influx?

• Chloride ion flux assay in cultured neurons or oocytes
• Tail-flick nociception test
• Elevated plus maze behavioral assay
• Actophotometer locomotor count

Correct Answer: Chloride ion flux assay in cultured neurons or oocytes

Q9. Which EEG change is most characteristic of hypnotic-induced sleep in animal models?

• Increase in low-frequency (delta) power and sleep spindles
• Increase in high-frequency (gamma) activity
• Marked desynchronization and wakefulness patterns
• Loss of all rhythmic activity without sleep structure

Correct Answer: Increase in low-frequency (delta) power and sleep spindles

Q10. A novel compound increases the ED50 for pentobarbital-induced sleep when co-administered. This suggests the compound is likely to be a:

• Pentobarbital antagonist or inhibitor of pentobarbital action
• Synergistic hypnotic potentiator
• Benzodiazepine receptor agonist
• GABA uptake inhibitor increasing pentobarbital effect

Correct Answer: Pentobarbital antagonist or inhibitor of pentobarbital action

Q11. Which test is best to screen anxiolytic activity often overlapping with sedative properties?

• Elevated plus maze
• Pentobarbital-induced sleeping time test
• Rotarod test
• Forced swim test

Correct Answer: Elevated plus maze

Q12. During screening, which observation would indicate a sedative with significant respiratory depression risk?

• Marked decrease in respiratory rate and oxygen saturation
• Increased exploratory behavior in open field
• Improved rotarod performance
• Reduced anxiety-like behavior without respiratory change

Correct Answer: Marked decrease in respiratory rate and oxygen saturation

Q13. Which animal species is most commonly used in initial screening of sedatives and hypnotics due to availability and well-characterized responses?

• Mouse
• Dog
• Non-human primate
• Guinea pig

Correct Answer: Mouse

Q14. In receptor pharmacology, a positive allosteric modulator of GABA-A receptors typically does which of the following?

• Enhances GABA-induced chloride influx without directly activating the receptor
• Blocks GABA binding and inhibits chloride influx
• Directly opens the chloride channel in absence of GABA
• Irreversibly inactivates the receptor

Correct Answer: Enhances GABA-induced chloride influx without directly activating the receptor

Q15. What is the primary experimental endpoint in an actophotometer or automated locomotor activity test used during sedative screening?

• Total counts of movement indicating spontaneous activity level
• Latency to fall from an elevated beam
• Number of open-arm entries in a maze
• Duration of sleep after hypnotic challenge

Correct Answer: Total counts of movement indicating spontaneous activity level

Q16. Which result would indicate a drug has muscle-relaxant properties rather than pure sedation when tested on rotarod and grip-strength assays?

• Impaired rotarod performance with decreased grip-strength
• Prolonged pentobarbital sleep time without motor impairment
• Increased open-arm time in elevated plus maze only
• No change in locomotor counts but increased exploratory head-dips

Correct Answer: Impaired rotarod performance with decreased grip-strength

Q17. When establishing ED50 in an animal screening study, what is being determined?

• The dose producing the defined pharmacological effect in 50% of animals
• The dose that kills 50% of animals
• The maximal effect achievable at any dose
• The dose producing side effects in 50% of animals

Correct Answer: The dose producing the defined pharmacological effect in 50% of animals

Q18. Which screening model helps distinguish sedative (reduced activity) from anxiolytic (increased open-arm exploration) effects?

• Combination of open-field/actophotometer and elevated plus maze
• Pentobarbital sleep test alone
• Rotarod test alone
• EEG recording alone

Correct Answer: Combination of open-field/actophotometer and elevated plus maze

Q19. In vitro autoradiography mapping of GABA-A receptor density is especially useful for which purpose in screening?

• Visualizing regional receptor binding and drug distribution in brain slices
• Measuring whole-animal sleep duration
• Assessing motor coordination effects
• Recording live EEG in behaving animals

Correct Answer: Visualizing regional receptor binding and drug distribution in brain slices

Q20. Which behavioral sign during an acute sedative screen warns of excessive CNS depression beyond therapeutic effect?

• Loss of righting reflex or deep sedation beyond arousability
• Mild reduction in exploratory activity
• Transient increase in grooming
• Short, reversible ataxia only

Correct Answer: Loss of righting reflex or deep sedation beyond arousability

Q21. Which test is often used to assess anticonvulsant activity and can indicate interaction with sedative/hypnotic mechanisms?

• Pentylenetetrazol (PTZ) seizure threshold test
• Rotarod coordination test
• Open-field locomotion
• Light–dark box

Correct Answer: Pentylenetetrazol (PTZ) seizure threshold test

Q22. A compound that increases benzodiazepine receptor binding but fails to enhance GABAergic chloride influx most likely acts as a:

• Neutral ligand or antagonist at the benzodiazepine site
• Full positive allosteric modulator of GABA-A
• Direct GABA-A agonist opening channels independently
• Non-specific sedative depressing metabolic rate

Correct Answer: Neutral ligand or antagonist at the benzodiazepine site

Q23. Which methodological consideration reduces bias in behavioral screening studies for sedatives and hypnotics?

• Blinding of observer and randomization of treatment groups
• Using only one animal per treatment group
• Allowing the investigator to choose groups based on appearance
• Measuring endpoints only once at study end

Correct Answer: Blinding of observer and randomization of treatment groups

Q24. Which combination of mechanisms explains how barbiturates produce hypnotic effects differently from benzodiazepines?

• Barbiturates increase duration of GABA-A channel opening and can directly activate receptor at high doses
• Barbiturates are selective benzodiazepine site agonists enhancing frequency of channel opening
• Barbiturates block GABA synthesis centrally
• Barbiturates act as opioid receptor agonists to induce sleep

Correct Answer: Barbiturates increase duration of GABA-A channel opening and can directly activate receptor at high doses

Q25. In pharmacokinetic screening relevant to sedatives, which property most influences onset time of hypnotic action after intravenous dosing?

• Rate of brain penetration (lipophilicity and blood–brain barrier permeability)
• Protein binding in peripheral tissues only
• Hepatic clearance after renal excretion complete
• Renal clearance rate exclusively

Correct Answer: Rate of brain penetration (lipophilicity and blood–brain barrier permeability)

Q26. Which outcome in an elevated plus maze indicates an anxiolytic-like action that may accompany sedative effects?

• Increased time and entries into open arms
• Decreased time in closed arms only
• Reduced total arm entries without change in open-arm time
• Increased freezing behavior

Correct Answer: Increased time and entries into open arms

Q27. When using EEG to evaluate sleep architecture after a test hypnotic, which stage change suggests improved sleep consolidation?

• Increased non-REM slow-wave (delta) sleep and decreased awakenings
• Marked increase in REM activity only
• Greater fragmentation with frequent brief arousals
• Complete suppression of REM and non-REM without continuity

Correct Answer: Increased non-REM slow-wave (delta) sleep and decreased awakenings

Q28. Which in vitro approach helps predict whether a compound will act as a benzodiazepine-site ligand before animal testing?

• Competitive radioligand displacement assay at benzodiazepine binding site
• Pentobarbital sleep test in mice
• Rotarod motor coordination assay
• Open-field locomotor activity in rats

Correct Answer: Competitive radioligand displacement assay at benzodiazepine binding site

Q29. For translation to human safety, which preclinical finding would most strongly raise concern for combination use with alcohol?

• Marked potentiation of pentobarbital-induced sleep and respiratory depression
• Minor decrease in locomotor activity without physiologic changes
• Selective increase in exploratory behavior
• Reversed effects by flumazenil only

Correct Answer: Marked potentiation of pentobarbital-induced sleep and respiratory depression

Q30. In designing a screening battery for sedatives/hypnotics, which combination offers broad evaluation of efficacy and safety?

• Pentobarbital sleep test, rotarod, open-field/actophotometer, EEG sleep recording and receptor binding
• Only rotarod and grip-strength tests
• Only in vitro binding studies without behavioral tests
• Only EEG monitoring without behavioral assessment

Correct Answer: Pentobarbital sleep test, rotarod, open-field/actophotometer, EEG sleep recording and receptor binding

G S Sachin

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.

Mail- Sachin@pharmacyfreak.com