Screening models for CNS activity and antipsychotic agents are essential topics for B.Pharm students preparing for research or clinical roles. This introduction covers key concepts such as in vitro receptor binding assays, radioligand studies, blood–brain barrier penetration, in vivo behavioral models (e.g., conditioned avoidance response, apomorphine- and amphetamine-induced hyperactivity, prepulse inhibition), pharmacokinetics, and safety screens for extrapyramidal and metabolic side effects. Understanding predictive validity, translational biomarkers, and screening cascades helps you interpret preclinical data and optimize lead selection. Mastery of these models informs rational drug design and regulatory expectations. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which in vivo behavioral model is most commonly used to predict antipsychotic efficacy by measuring blockade of operant avoidance behavior?
- Forced swim test
- Conditioned avoidance response
- Rotarod test
- Open field test
Correct Answer: Conditioned avoidance response
Q2. Which receptor antagonism is most closely associated with the therapeutic effects of typical antipsychotics?
- 5-HT1A receptor antagonism
- Dopamine D2 receptor antagonism
- NMDA receptor antagonism
- GABA-A receptor agonism
Correct Answer: Dopamine D2 receptor antagonism
Q3. Which preclinical test is primarily used to assess extrapyramidal side effect liability (catalepsy) of antipsychotic candidates?
- Apomorphine-induced climbing
- Conditioned place preference
- Bar test (catalepsy test)
- Pretreatment locomotor habituation
Correct Answer: Bar test (catalepsy test)
Q4. Radioligand binding assays in vitro primarily measure which parameter for receptor-ligand interactions?
- Blood–brain barrier penetration
- Half-life in plasma
- Binding affinity (Ki or Kd)
- Functional agonist efficacy
Correct Answer: Binding affinity (Ki or Kd)
Q5. Prepulse inhibition (PPI) of the acoustic startle reflex is a screening model for which schizophrenia-related deficit?
- Impaired sensorimotor gating
- Memory consolidation
- Motor coordination
- Anxiety-like behavior
Correct Answer: Impaired sensorimotor gating
Q6. Amphetamine-induced hyperlocomotion in rodents is used to screen antipsychotics because it models hyperactivity driven primarily by which neurotransmitter system?
- Serotonergic system
- GABAergic system
- Glutamatergic system
- Dopaminergic system
Correct Answer: Dopaminergic system
Q7. Which in vitro assay helps predict whether a candidate antipsychotic will cross the blood–brain barrier via passive diffusion?
- PAMPA-BBB (parallel artificial membrane permeability assay)
- hERG channel binding assay
- Rotarod performance
- Forced swim immobility
Correct Answer: PAMPA-BBB (parallel artificial membrane permeability assay)
Q8. Atypical antipsychotics are often characterized by higher affinity for which receptor relative to D2 that may reduce EPS?
- 5-HT2A receptor
- NMDA receptor
- Alpha-1 adrenergic receptor
- Histamine H1 receptor
Correct Answer: 5-HT2A receptor
Q9. Microdialysis in awake animals is a technique used in CNS screening to measure what?
- Brain electrical activity
- Extracellular neurotransmitter levels
- Behavioral despair
- Protein folding in neurons
Correct Answer: Extracellular neurotransmitter levels
Q10. Which safety pharmacology assay screens for cardiac risk that is important during antipsychotic development?
- hERG channel inhibition assay
- Elevated plus maze
- Novel object recognition
- PPI test
Correct Answer: hERG channel inhibition assay
Q11. In radioligand autoradiography, what information can you obtain relevant to antipsychotic discovery?
- Whole-body pharmacokinetics
- Regional brain receptor distribution and density
- Metabolic enzyme induction in liver
- Behavioral changes in rodents
Correct Answer: Regional brain receptor distribution and density
Q12. Which test is commonly used to evaluate cognitive effects (working memory) relevant to antipsychotic treatment in rodents?
- Tail suspension test
- Novel object recognition or Y-maze
- Hot plate test
- Apomorphine-induced stereotypy
Correct Answer: Novel object recognition or Y-maze
Q13. Ki value in a receptor binding assay represents:
- The intrinsic activity of a ligand
- The concentration of ligand that blocks 50% of specific binding
- The dissociation constant indicating binding affinity
- The half-life of ligand in plasma
Correct Answer: The dissociation constant indicating binding affinity
Q14. Which animal model uses PCP or ketamine to produce schizophrenia-like symptoms for screening novel antipsychotics?
- Monoamine depletion model
- NMDA receptor antagonist-induced model
- Social defeat stress model
- Transgenic APP mouse model
Correct Answer: NMDA receptor antagonist-induced model
Q15. In early screening cascades, which ADME parameter is most critical to ensure candidate reaches CNS at therapeutic levels?
- Renal clearance
- Plasma protein binding only
- Brain-to-plasma ratio (CNS exposure)
- Gastrointestinal transit time
Correct Answer: Brain-to-plasma ratio (CNS exposure)
Q16. Which behavioral test is least appropriate to directly evaluate antipsychotic-like activity?
- Conditioned avoidance response
- Apomorphine-induced climbing
- Forced swim test
- Amphetamine-induced hyperlocomotion
Correct Answer: Forced swim test
Q17. Functional assays such as cAMP accumulation or calcium mobilization are used to assess what property of a ligand?
- Passive diffusion across membranes
- Functional agonist/antagonist activity at a receptor
- Protein binding in plasma
- Electrophysiological conduction velocity
Correct Answer: Functional agonist/antagonist activity at a receptor
Q18. PET imaging in preclinical antipsychotic research is primarily used to:
- Monitor liver toxicity
- Visualize receptor occupancy and brain distribution
- Measure in vitro binding kinetics only
- Replace behavioral testing entirely
Correct Answer: Visualize receptor occupancy and brain distribution
Q19. A compound that produces potent D2 blockade but high catalepsy in rodents is most likely to cause which adverse effect in humans?
- Metabolic syndrome
- Extrapyramidal symptoms (EPS)
- Hypotension
- Anticholinergic delirium
Correct Answer: Extrapyramidal symptoms (EPS)
Q20. Which in vitro screen helps predict whether a drug candidate will be a substrate or inhibitor of P-glycoprotein at the blood–brain barrier?
- Caco-2 cell permeability assay
- Rotarod test
- Tail flick assay
- Forced swim test
Correct Answer: Caco-2 cell permeability assay
Q21. The conditioned place preference (CPP) assay is primarily used to assess which property of CNS drugs?
- Antipsychotic efficacy
- Abuse potential or rewarding effects
- Antiepileptic activity
- Antidepressant-induced neurogenesis
Correct Answer: Abuse potential or rewarding effects
Q22. Electrophysiological recordings (EEG) in preclinical screening can help detect which early effect of CNS-active drugs?
- Changes in synaptic currents and network oscillations
- Plasma protein binding
- Hepatotoxic metabolites
- Renal clearance rate
Correct Answer: Changes in synaptic currents and network oscillations
Q23. Selectivity profiling across receptor panels is important because off-target binding to which receptor commonly causes sedation and weight gain?
- Dopamine D3 receptor
- Histamine H1 receptor
- M1 muscarinic receptor
- NMDA receptor
Correct Answer: Histamine H1 receptor
Q24. In a drug discovery cascade, which model has the highest predictive validity for antipsychotic clinical efficacy?
- In vitro receptor binding only
- Conditioned avoidance response and clinical receptor occupancy data combined
- Forced swim test alone
- Single-dose rotarod test
Correct Answer: Conditioned avoidance response and clinical receptor occupancy data combined
Q25. Which metabolic liability screening is critical due to the association of some antipsychotics with severe weight gain and diabetes?
- hERG binding only
- Assessment of effects on glucose homeostasis and lipid metabolism in chronic models
- PAMPA permeability only
- Acute nociception assays
Correct Answer: Assessment of effects on glucose homeostasis and lipid metabolism in chronic models
Q26. Which molecule property most favors passive BBB penetration for CNS drugs?
- High polar surface area and multiple charges
- Low lipophilicity and high molecular weight
- Moderate lipophilicity and low polar surface area
- High P-glycoprotein efflux susceptibility
Correct Answer: Moderate lipophilicity and low polar surface area
Q27. Which behavioral measure is frequently used to screen antipsychotic drugs for their ability to reverse social withdrawal in animal models?
- Social interaction test
- Hot plate test
- Grip strength test
- Light/dark box
Correct Answer: Social interaction test
Q28. When interpreting receptor occupancy studies for D2 antagonists, what occupancy range is typically associated with antipsychotic efficacy and minimal extra pyramidal side effects?
- 10–20% occupancy
- >90% occupancy
- 60–80% occupancy
- 0% occupancy
Correct Answer: 60–80% occupancy
Q29. Which of the following is a translational biomarker used to link preclinical findings to clinical outcomes in antipsychotic development?
- Rodent tail flick latency
- Plasma enzyme levels unrelated to CNS
- D2 receptor occupancy measured by PET
- Mouse fur color changes
Correct Answer: D2 receptor occupancy measured by PET
Q30. Which statement best describes the role of high-throughput in vitro screens in early CNS antipsychotic discovery?
- They replace all in vivo testing for regulatory approval
- They prioritize compounds by binding affinity, off-target profile, and basic ADME to reduce later attrition
- They are not useful for CNS drugs due to complexity of the brain
- They only measure behavioral efficacy directly
Correct Answer: They prioritize compounds by binding affinity, off-target profile, and basic ADME to reduce later attrition
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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