PCOL 6-1 Genetic techniques in neuropharmacology ~ 6-2 Behavioural Neuropharmacology
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Questions and Answers

Which method is used to identify genes/proteins involved in specific physiological or pathological pathways?

  • Transgenic
  • Conditional knockout
  • Knock-in (point mutation)
  • Knockout (correct)
  • Which genetically engineered model is used for lead generation and refinement?

  • Knock-in (reporter) (correct)
  • Conditional knockout
  • Transgenic
  • Knockout
  • Which genetically engineered model is used for preclinical development to test safety and efficacy?

  • Transgenic (correct)
  • Knockout
  • Conditional knockout
  • Humanized model
  • What is the advantage of using rodent models in research?

    <p>They have well-validated models for human diseases</p> Signup and view all the answers

    What is homologous recombination used for in making rodent models?

    <p>To exchange genetic material between two strands of DNA</p> Signup and view all the answers

    Which system allows for tissue-specific genetic changes and can control the location and timing of gene modifications?

    <p>Cre-Lox System</p> Signup and view all the answers

    What is required for the Cre-Lox System to work in cells?

    <p>Expression of both Cre and LoxP</p> Signup and view all the answers

    Which type of virus particles are commonly used as viral vectors?

    <p>Non-genetically modified virus particles</p> Signup and view all the answers

    What is the advantage of using promoters in viral vectors?

    <p>They help target specific cell types</p> Signup and view all the answers

    What is the purpose of using Cre-Lox in targeting Gly neurons in a small region of the spinal cord?

    <p>To prevent neuron firing</p> Signup and view all the answers

    Which technique is used to selectively turn on/off specific neuron subtypes using light?

    <p>Optogenetics</p> Signup and view all the answers

    What is the purpose of using designer drugs in chemogenetics?

    <p>To selectively turn on/off specific neuron subtypes</p> Signup and view all the answers

    Which gene has been identified as a possible target for transdermal analgesics vs anti-itch treatments?

    <p>GPCR MrgprA3+</p> Signup and view all the answers

    Which of the following is NOT one of the validity criteria of an animal model?

    <p>Genetic validity</p> Signup and view all the answers

    What is the purpose of the 3 R's in animal research?

    <p>To minimize the use of animals</p> Signup and view all the answers

    Which of the following is a consideration for animal research ethics?

    <p>Animal welfare</p> Signup and view all the answers

    What does face validity of an animal model refer to?

    <p>The resemblance of the animal model's response to that observed in humans</p> Signup and view all the answers

    Which of the following is NOT one of the 3 R's in animal research?

    <p>Reconciliation</p> Signup and view all the answers

    Which type of models use natural conflict for a rodent to explore a novel environment?

    <p>Exploratory models</p> Signup and view all the answers

    Which disorder is not classified as an anxiety/mood disorder?

    <p>Post-Traumatic Stress Disorder (PTSD)</p> Signup and view all the answers

    What percentage of patients does exposure therapy effectively treat in PTSD?

    <p>56%</p> Signup and view all the answers

    Which symptoms are involved in modelling depression?

    <p>Apathy</p> Signup and view all the answers

    Which test is commonly used to assess learned helplessness in animal models of depression?

    <p>Tail suspension test</p> Signup and view all the answers

    Which type of symptoms in schizophrenia are associated with hyperactivity, stereotypy, and cognitive impairment in animal models?

    <p>Positive symptoms</p> Signup and view all the answers

    Which of the following is NOT a negative symptom of schizophrenia that can be studied in animal models?

    <p>Anhedonia</p> Signup and view all the answers

    Which test is commonly used to assess attention and startle response inhibition in animal models of cognitive symptoms in schizophrenia?

    <p>Pre-pulse inhibition of startle</p> Signup and view all the answers

    Which protein is upregulated in schizophrenia and is considered a risk gene?

    <p>Complement-4</p> Signup and view all the answers

    What is the mechanism by which THC exposure reduces the neurobehavioral effects of risperidone?

    <p>By increasing the action of P-gp to remove risperidone from the brain</p> Signup and view all the answers

    Which gene may be linked to schizophrenia and is associated with hyperactivity, PPI deficits, and cognitive deficits?

    <p>Nrg1</p> Signup and view all the answers

    Which medication can reverse hyperactivity caused by Nrg1 in animal models?

    <p>Clozapine</p> Signup and view all the answers

    Which receptors show altered expression in the nucleus accumbens in animal models of schizophrenia?

    <p>D2, 5-HT2A, and NMDA receptors</p> Signup and view all the answers

    Study Notes

    Gene and Protein Identification

    • Methods such as gene knockout and transgenic models are used to identify genes/proteins involved in specific physiological or pathological pathways.

    Genetically Engineered Models

    • Knockout mouse models are commonly used for lead generation and refinement; they provide insights into gene function.
    • Transgenic mouse models are utilized for preclinical development to test safety and efficacy of therapeutic agents.

    Advantages of Rodent Models

    • Rodent models offer advantages such as genetic similarity to humans, short lifespan, and controlled breeding, allowing for consistent experimental conditions.

    Homologous Recombination

    • This technique is employed to create precise genetic alterations in rodent models, enabling the study of gene functions and disease pathways.

    Cre-Lox System

    • Allows for tissue-specific genetic modifications; it can control the location and timing of gene alterations, facilitating targeted genetic research.

    Requirements for Cre-Lox System

    • The presence of Cre recombinase and LoxP sites in the target cells is essential for successful gene modification.

    Viral Vectors

    • Lentiviral vectors are commonly used due to their ability to infect both dividing and non-dividing cells.

    Promoters in Viral Vectors

    • Using promoters in viral vectors enhances the specificity and expression level of transgenes, improving the effectiveness of gene delivery.

    Purpose of Cre-Lox in Targeting Gly Neurons

    • Cre-Lox is used to precisely target and manipulate Gly neurons in a small spinal cord region, advancing our understanding of neuronal functions.

    Optogenetics

    • This technique selectively turns on/off specific neuron subtypes using light, allowing for precise control of neuronal activity in research.

    Designer Drugs in Chemogenetics

    • Designer drugs are utilized to selectively activate or inhibit specific neurons, facilitating experimental manipulation of specific neuronal circuits.

    Target for Transdermal Analgesics and Anti-Itch Treatments

    • The gene identified as a possible target for these treatments is known for its role in modulating pain and itch sensations.

    Validity Criteria of Animal Models

    • Key validity criteria include face validity, construct validity, and predictive validity; however, "efficacy" is not a validity criterion.

    The 3 R's in Animal Research

    • The 3 R's refer to Replacement, Reduction, and Refinement, representing ethical principles aimed at improving animal research practices.

    Ethical Considerations in Animal Research

    • Ethical considerations include animal welfare, the necessity of research, and minimizing pain and distress in experimental subjects.

    Face Validity of Animal Models

    • Face validity refers to the extent to which an animal model replicates the symptoms and behaviors observed in human conditions.

    Natural Conflict Models

    • Models utilizing natural conflict allow rodents to explore novel environments, providing insights into anxiety and decision-making processes.

    Non-Anxiety Disorder Classification

    • Disorders such as schizophrenia are not classified as anxiety/mood disorders.

    Exposure Therapy Effectiveness in PTSD

    • Exposure therapy effectively treats around 60-80% of patients with PTSD.

    Symptoms Involved in Depression Modeling

    • Symptoms include anhedonia, fatigue, and changes in sleep patterns, which are critical for modeling depression.

    Learned Helplessness Test in Depression

    • The Forced Swim Test is commonly used to assess learned helplessness in animal models of depression.

    Schizophrenia Symptoms in Animal Models

    • Symptoms associated with hyperactivity, stereotypy, and cognitive impairment are examined to better understand cognitive deficits in schizophrenia.

    Negative Symptoms of Schizophrenia

    • Apathy, social withdrawal, and lack of motivation are negative symptoms studied; however, "euphoria" is not considered a negative symptom.

    Cognitive Symptoms Assessment in Schizophrenia

    • The Prepulse Inhibition (PPI) test is frequently employed to assess attention and startle response inhibition in models of schizophrenia.

    Schizophrenia Risk Gene

    • The protein associated with increased risk in schizophrenia is upregulated and has been linked to various behavioral deficits.

    THC and Risperidone Mechanism

    • THC reduces the neurobehavioral effects of risperidone by modulating neurotransmitter levels, potentially alleviating some side effects.

    Gene Linked to Schizophrenia

    • The Nrg1 gene is associated with hyperactivity, PPI deficits, and cognitive deficits, suggesting its role in schizophrenia.

    Medication Reversing Hyperactivity in Animal Models

    • Specific antipsychotic agents can reverse hyperactivity caused by Nrg1 mutations, illustrating potential treatment strategies.

    Receptor Alterations in Schizophrenia Models

    • Altered expression of dopamine receptors is observed in the nucleus accumbens in animal models, providing insights into the neurobiology of schizophrenia.

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    Description

    Test your knowledge on target discovery, target validation, and lead generation in the field of genetics and molecular biology. Learn about techniques such as knockout, conditional knockout, knock-in point mutation, and transgenic approaches. Explore how these methods are used to identify genes and proteins involved in specific physiological or pathological pathways, confirm their role in relieving associated phenotypes, and assess in vivo stability and tissue specificity.

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