Introduction: Screening for CNS stimulants and depressants, anxiolytics, antipsychotics MCQs With Answer is designed for M.Pharm students to reinforce advanced concepts in pharmacological and toxicological screening methods. This set focuses on behavioral, biochemical and analytical assays used in preclinical evaluation — including locomotor tests, anxiety and depression paradigms, seizure models, receptor binding, uptake assays, chromatographic confirmation, safety screens and interpretation of dose-response parameters. Questions emphasize method selection, end-point interpretation, mechanism-specific assays and regulatory/ethical considerations crucial for reliable screening. Use these MCQs to prepare for exams and practical screening design by testing deeper comprehension of which tests are appropriate for specific CNS pharmacologies and toxicities.
Q1. Which behavioral test is most commonly used to screen CNS stimulants by measuring spontaneous ambulatory activity in rodents?
- Elevated plus maze measuring open arm entries
- Rotarod performance test
- Open field locomotor activity test
- Forced swim immobility test
Correct Answer: Open field locomotor activity test
Q2. Which screening method is typically used to detect sedative-hypnotic properties by measuring potentiation of sleep induced by a barbiturate?
- Pentylenetetrazol seizure threshold test
- Pentobarbital-induced sleep time assay
- Conditioned place preference test
- Tail flick nociception test
Correct Answer: Pentobarbital-induced sleep time assay
Q3. Anxiolytic-like activity in rodents is most reliably indicated by which change in the elevated plus maze?
- Decreased number of open arm entries
- Increased percentage of time spent in open arms
- Reduced total arm entries without arm preference
- Increased number of head dips in closed arms only
Correct Answer: Increased percentage of time spent in open arms
Q4. The tail suspension test is primarily used to screen compounds for which neuropsychopharmacological activity?
- Anxiolytic activity
- Antipsychotic activity
- Antidepressant activity
- Anticonvulsant activity
Correct Answer: Antidepressant activity
Q5. Which seizure model is commonly used to evaluate drugs that enhance GABAergic inhibition and to screen for anticonvulsant activity?
- Maximal electroshock seizure (MES) test only
- Pentylenetetrazol (PTZ)-induced seizure test
- Forced swim-induced convulsion test
- Conditioned place aversion test
Correct Answer: Pentylenetetrazol (PTZ)-induced seizure test
Q6. Which in vitro technique directly measures affinity of a test compound for a specific neurotransmitter receptor?
- Open field locomotor assay
- Radioligand binding assay
- Elevated plus maze
- Pentobarbital sleep potentiation
Correct Answer: Radioligand binding assay
Q7. In the forced swim test, a compound showing antidepressant-like activity will typically produce which behavioral change?
- Increase in immobility time
- Decrease in immobility time
- Increase in grooming without locomotion changes
- Reduction in swimming but increased climbing only
Correct Answer: Decrease in immobility time
Q8. To assess the abuse potential of a novel stimulant, which preclinical assay is most appropriate?
- Rotarod motor coordination test
- Conditioned place preference paradigm
- Pentobarbital-induced sleep test
- hERG channel inhibition assay
Correct Answer: Conditioned place preference paradigm
Q9. Which test is sensitive to motor impairment caused by CNS depressants and some antipsychotics, and measures fall latency?
- Elevated plus maze
- Rotarod performance test
- Open field rearing count
- Tail suspension test
Correct Answer: Rotarod performance test
Q10. Which behavioral assay is used to determine whether a test drug produces subjective effects similar to a known psychotropic by training animals to distinguish drug vs vehicle?
- Drug discrimination assay
- Irwin observational battery
- Pentylenetetrazol seizure threshold
- Pre-pulse inhibition of startle
Correct Answer: Drug discrimination assay
Q11. For confirmatory identification and quantification of CNS drugs and metabolites in plasma, which analytical technique is preferred for sensitivity and specificity?
- Thin-layer chromatography with UV detection
- Enzyme-linked immunosorbent assay (ELISA)
- Liquid chromatography–tandem mass spectrometry (LC-MS/MS)
- Paper chromatography
Correct Answer: Liquid chromatography–tandem mass spectrometry (LC-MS/MS)
Q12. Preclinical safety screening for antipsychotics often includes assessing risk for QT prolongation through which in vitro assay?
- Monoamine oxidase inhibition assay
- hERG potassium channel inhibition assay
- Dopamine transporter uptake assay
- Forced swim test
Correct Answer: hERG potassium channel inhibition assay
Q13. In pharmacological screening, ED50 is best defined as which of the following?
- The dose that produces lethal effects in 50% of animals
- The dose that produces a therapeutic effect in 50% of the population
- The dose that completely inhibits a receptor in 50% of assays
- The dose that produces side effects in 50% of animals
Correct Answer: The dose that produces a therapeutic effect in 50% of the population
Q14. The therapeutic index (TI) in preclinical screening is commonly calculated as which ratio?
- ED50 divided by LD50
- LD50 divided by ED50
- NOAEL divided by LOAEL
- IC50 divided by EC50
Correct Answer: LD50 divided by ED50
Q15. Which in vitro assay would you select to screen for stimulant activity mediated by inhibition of dopamine uptake?
- Serotonin receptor binding autoradiography
- Dopamine transporter (DAT) uptake inhibition assay
- hERG channel patch clamp
- Glutamate NMDA receptor electrophysiology
Correct Answer: Dopamine transporter (DAT) uptake inhibition assay
Q16. The primary mechanism by which benzodiazepines exert anxiolytic effects in screening assays is:
- Direct agonism of dopamine D2 receptors
- Inhibition of serotonin reuptake transporter
- Positive allosteric modulation of GABA-A receptors
- Antagonism of NMDA receptors
Correct Answer: Positive allosteric modulation of GABA-A receptors
Q17. Which ethical principle set is most relevant when designing animal screening studies for CNS-active drugs to minimize harm?
- ALARP (As Low As Reasonably Practicable)
- Good Laboratory Practice (GLP) only
- The 3Rs: Replacement, Reduction, Refinement
- GMP (Good Manufacturing Practice)
Correct Answer: The 3Rs: Replacement, Reduction, Refinement
Q18. The Irwin test (or Functional Observational Battery) is used in acute screening primarily to detect which of the following?
- Specific receptor binding affinity
- Gross behavioral and physiological signs of neurotoxicity
- Long-term antidepressant efficacy
- hERG channel inhibition
Correct Answer: Gross behavioral and physiological signs of neurotoxicity
Q19. Which preclinical behavioral paradigm is widely used as a model for sensorimotor gating deficits relevant to schizophrenia and to assess antipsychotic efficacy?
- Pre-pulse inhibition (PPI) of the acoustic startle response
- Open field thigmotaxis index
- Pentobarbital sleep latency
- Conditioned taste aversion
Correct Answer: Pre-pulse inhibition (PPI) of the acoustic startle response
Q20. For initial high-throughput screening of potential CNS-active small molecules, which strategy balances speed and biological relevance before detailed in vivo testing?
- Direct in vivo chronic toxicity studies in primates
- High-throughput receptor binding and transporter uptake assays followed by targeted cell-based functional assays
- Only immunoassay screening of plasma samples
- Exclusive use of behavioral assays without in vitro profiling
Correct Answer: High-throughput receptor binding and transporter uptake assays followed by targeted cell-based functional assays

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