PSYCH 454 - Exam II

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PSYCH 454 - Exam II
2011-06-20 19:33:55
Research methods models addiction abuse alcohol opiates cannabinoids

Research Methods, Models of Addiction/Drug Abuse, Alcohol, Opiates, Cannabinoids
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  1. What are four things that can be implanted using stereotaxic surgery and what are each of them used for?
    • Cannula (hollow tube) - used for localized infusions
    • Injector - used for electrical or neurotoxic leisons
    • Dialysis Probe - used to analysize NT concentrations
    • Electrode - used to record action potentials
  2. What are a couple of different methods used for leisoning brain areas in research rodents?
    • Electrolytic - "burn" out tissue with high electrical current
    • Neurotoxic- inject neurotoxin through a cannula;
    • general neurotoxins = kainic acid and ibotenic acid
    • specific neurotoxins = 6-hydroxydopamine
  3. ____________ is a technique used to measure NT released in vivo; cerebrospinal fluid is collected from the extracellular space and analyzed by _______________________; which seperates molecules by size and charge.
    Microdialysis; high-performance liquid chromatography
  4. T/F Microdialysis techniques can be performed while the animal is awake and engaged in behavioral tasks.
  5. What technique involves electrically stimulating cells at the tip of an electrode?
  6. What type of electrophysiology allows for recording from a single neuron while the animal is anesthetized? What type allows for monitoring neurons during behavior?
    • Intracellular electrophysiology
    • Extracellular electrophysiology
  7. What type of electrophysiology allows researchers to record membrane potentials and the activity of individual ion channels within a neuron? How is this usually accomplished?
    • Patch Clamp Recording
    • Cellular activity is recorded in a culture or from a brain slice with a micropipette that seals with the neuron membrane
  8. What are three different techniques used to localize specific proteins in specific brain regions? How are the proteins or their precursors identified?
    • Immunocytochemistry
    • In situ hybridization
    • DNA microarrays
    • They are tagged with flourescent antibody
  9. ______________ is used to tag specific proteins and monitor their activity after manipulation, while ______________ is used to tag specific mRNAs and quantify changes in their levels after manipulation.
    • Immunocytochemistry
    • In situ hybridization
  10. What class of research techniques requires fixation of the brain using a preservative such as formaldehyde?
    Localization techniques (ICC, ISH, DNA microarray)
  11. DNA microarrays are a way to measure large-scale patterns of gene expression before/after a manipulation. What is the problem with this technique and how can this be compensated for?
    Lots of error when analyzing 1,000s of mRNA molecules at once; have to verify significant findings using ICC or ISH
  12. What two forms of brain imaging are used to study/examine the structure of the brain? What two forms are used to study the function of the brain?
    Computerized Tomography (CT Scan) & Magnetic Resonance Imaging (MRI)

    Positron Emisson Tomography (PET Scan) and Functional Magnetic Resonance Imaging (fMRI)
  13. Which imaging technique uses X-rays to generate "slices" of the brain?
    Computerized Tomography (CT Scan)
  14. What imaging technique measures resonance of hydrogen molecules (water) to create an image of the brain?
    Magnetic Resonance Imaging (MRI)
  15. What imaging technique involves injection of a radioactive isotope and subsequent measurement of brain activity via the gamma rays released as the isotope decays?
    Positron Emisson Tomography (PET)
  16. T/F PET scans have the greatest resolution of the functional imaging techniques discussed in class
    False (fMRI)
  17. What imaging technique allows for real-time monitoring of blood oxygen levels and flow in the brain?
    Functional Magnetic Resonance Imaging (fMRI)
  18. What were the two genetic engineering research methods discussed in class?
    • Gene knockouts
    • Transgenic mice
  19. _______________ is a technique that allows researchers to eliminate a gene and its protein from an animal in order to see what happens when that gene/protein is not present.
    Gene knockout
  20. What technique involves transfering of a gene from one species to another in order to better understand the function of the gene and create animal models of a disease or disorder?
    Transgenetic manipulations (gene replacement)
  21. What are three techniques used to study behavioral pharmacology? Describe them briefly.
    • Conditioned place preference
    • Drug self-administration
    • Measuring locomotor activity
  22. Why is drug seeking/taking perpetuated according to the physical dependence model?
    Maintained by the motivation to avoid withdrawal symptoms
  23. Abraham Wikler described a conditioned withdrawal response in his study of heroin addicts. What does this mean?
    Addicts associate a specfic environment with the experience of withdrawal symptoms and return to this environment can trigger the re-experience of withdrawal symptoms.
  24. Childress and O'Brien described conditioned cravings in their studies of crack/cocain addicts. What does this mean?
    Addicts associate certain environmental cues with the "rush" of using crack/cocaine and when they were exposed to a video showing the aquisition and use of cocaine they felt a conditioned rush or high
  25. Why is drug seeking/taking perpetuated according to the positive reinforcement model?
    Drug use reinforces whatever proceeding behavior was performed by producing euphoria. Abstinence creates feelings of craving for euphoria resulting in relapse.
  26. According to the _______________ model of addiction, a strong affective response (like that produced by a drug) automatically provokes and opposing affective response (like that produced by withdrawal).
    Opponent-Process Model
  27. According to the original opponent process model, repeated drug use increases the ____________ leading to increased experience of the _____________, and this promotes continued drug use.
    b-process; B-state
  28. According to the modified opponent process model, repeated drug use strengthens the __________, therefore drug use puts the user higher and higher in the _____________, however the baseline state shifts down placing the addict in the _________ when the drug is not present; this results in the experience of dysphoria without the drug.
    a-process; A-state; B-state
  29. What model suggests that repeated use of a drug increases wanting or craving for the drug, but does not increase actual enjoyment of the drug?
    Incentive-sensitization model
  30. According to the incentive sensitization model stimuli associated with drug use become extremely __________ and develop _________ properties.
    salient; incentive
  31. What are the benefits to the physical disease model of addiction even if it is not entirely correct?
    This model removes social stigma from addiction and reduces the sense of guilt/learned helplessness in the recovering addict.
  32. Alcohol does not _________, but it is easily absorbed from the GI tract because it is able to cross membranes by ___________. Alcohol absorption is enhanced by __________ and delayed by __________.
    Ionize; passive diffusion; carbonation; a full stomach
  33. _____________ is 60% more active in men than women and inhibited completely by _______.
    Alcohol dehydrogenase; aspirin
  34. Which component in the metabolism of alcohol is toxic and responsible for feeling sick if you drink too much? What enzyme breaks this molecule down?
    Acetaldehyde; acetaldehyde dehydrogenase
  35. ***List and describe the four forms of alcohol tolerance described in class.***
    • Acute tolerance - "drinking yourself sober", compensatory effects occur w/in a single exposure
    • Drug disposition tolerance - increased enzymes leads to more rapid alcohol metabolism
    • Pharmacodynamic tolerance - compensatory change in cell function (up/down regulation of receptors)
    • Behavioral Tolerance - "practice" effects, you get better at compensating for being drunk with repeated use
  36. What type of drug is alcohol? What other drugs in the same class can be used to eliminate withdrawal effects becasue of cross-dependence?
    Sedative-hypnotic; benzodiazapienes and barbituates
  37. What are three factors that contribute to acute alcohol toxicity (hangover)?
    Residual acetaldehye, gastric irritation, rebound drop in blood sugar
  38. Alcohol withdrawal begins ________ after cessasation and lasts ________.
    A few hours; 2-4 days
  39. ____________________ is the medical term that refers to the intense alcohol withdrawal symptoms (irritability, headache, confusion, convulsions, hallucinations, etc.) experienced by alcoholics upon cessation.
    Dellirium tremens
  40. Wernickee-Korsakoff Syndrome is commonly seen in alcoholics and caused by a ______________ deficiency. Initial symptoms include ________, ________, & ________ and as the syndrome progessess ___________.
    thiamine (vitamin-B1); confusion, tremors, poor coordination, memory disorder (alcoholics Alzheimers)
  41. Brain damage due to chronic alcoholism has profound effects including __________, _________ due to frontal lobe damage, __________ due to temporal lobe damage, and ___________ due to damage to the cerebellum.
    Enlarged ventricles; personality changes, memory loss, poor coordination (ataxia)
  42. Alcohol as upiquitous effects on the brain and for this reason and ethical reasons it can be very difficult to study in humans. Give four reasons why studying the effects of alcohol in animals offers a lot of insight.
    • Allows for a controlled environment
    • Allows for invasive techniques (damage, withdrawal, prenatal exposure)
    • Allows for genetic manipulations
    • Allows for screening of potential treatment strategies
  43. What are the four NT systems discussed in class that are affected by alcohol?
    Glutamatergic, GABAergic, Dopminergic, and the Opioid system
  44. Alcohol affects the glutamatergic system by inhibiting signaling at the _________ receptor causing _________. When consumed chronically these receptors ________ in number and this leads to ______________ and possibly _________ during withdrawal.
    NMDA, memory loss, increase, hyper-excitability, seizure
  45. Alcohol targets the _________ GABA receptor ________ the inhibitory effects of this system. When used chronically alcohol _________ GABA signaling and this also contributes to _____________ during withdrawal.
    GABAA, increasing, decreases, hyperexcitabilty
  46. Acutely, alcohol ________ the firing rate of dopamine neurons and the release of dopamine in the nucleus accumbens. During withdrawal dopamine release and firing are significantly ________ and this may explain the experience of _________.
    Increases; decreases; dysphoria
  47. Alcohol also has effects on the opioid system. Acutely, it __________ gene expression for opiod receptors. Chronically it __________ the concentration of these receptors in the brain.
    Increases, decreases
  48. Of the two types of alcoholism, ______ is genetically determined and results in heavy, often solitary drinking while _________ is more enviromentally determined and results in heavy, social drinking.
    Type II, Type I
  49. T/F Low sensitivity to the effects of alcohol increases risk of alcoholism
  50. What are the factors described in the 3-Factor Vulnerability Model of alcoholism
    • Psychological factors
    • Neurobiological factors
    • Sociocultural factors
  51. What seems to be the most effective form of treatment for alcoholism?
    A combination of community reinforcement programs and pharmacological medication
  52. What is the focus of the community reinforcement approach to treating alcoholism?
    Behavioral modification, discussion of problems associated with drinking, goal setting, community accountability
  53. What drug is used to make ingestion of alcohol unpleasant by inhibiting acetaldehyde dehydrogenase? What are the problems with this medication?
    Antabuse; low complaince, drinking on this drug increases risk of hepatitis
  54. What were the two drugs discussed in class that treat alcoholism by reducing its reinforcing qualities? What systems do they work on?
    • Naltrexone - opiate antagonist
    • Acamprosate - glutamate (partial NMDA) antagonist
  55. What are some of the effects of low, medium, and high doses of opiates?
    • Low - pain relief, mild respiratory depression, dreamy state, relief of psychological pain
    • Med - euphoria (users), dysphoria (non-users), nausea, vomiting
    • High - sedation, unconsciousness, hypothermia, severe respiratory depression (cause of overdose)
  56. What drug is used to treat someone overdosing on heroin or some other opiate? How does it work?
    Naltroxone - pure antagonist; outcompetes opiates for binding sites relieving severe respiratory depression and becasue of this precipatates withdrawal
  57. T/F Opiate receptors are ionotropic
  58. What five brain areas have the highest density of opiate receptors?
    Medial thalamus, locus coeruleus, raphae nuclei, periaqueductal grey, nucleus accumbens
  59. Which opiate receptor subtype has a wide distribution and is involved in analgesia, reinforcement, respiratory depression, and nausea?
  60. Which opiate receptor subtype is only distribted in the forebrain (motor integration, olfaction, cognitive function) and is important for modulating the analgesic and euphoric effects of the drug?
    δ receptor
  61. Which opiate receptor subtype has a limited distribution and is involved in pain perception and dysphoria, as well as water balance, feeding, temp. control, and neuroendocrine function? What does this receptor signal when activated?
    κ receptor; deviation from homeostasis
  62. Opiate receptors have inhibitory actions that are mediated by what four cellular changes?
    • Opening K+ channels (hyperpolarization, reduced firing)
    • Closing Ca2+ channels (decreased NT release)
    • Autoreceptor activation (decreased firing and NT release)
    • Inhibition of cAMP (tolerance, dependence, and withdrawal)
  63. T/F Rats allowed to self-administer opiates will slowly increase the amount they give themselves until reaching dangerous levels/overdose
    False - as in humans self-administration plateus and the users goal is only to keep receptors occupied, not over-occupied
  64. T/F The reinforcing effects of opiates are mediated by increased release of dopamine in the nucleus accumbens only.
    False - they are reinforced this way, but there is another yet unknown way as well because rats without a nucleus accumbens will continue to self-administer (at a slightly reduced rate)
  65. Opiate withdrawal peaks ________ after cessastion and the intense, extremely unpleasant effects continute for _________.
    36-48 hours, 7-10 days
  66. Opiate withdrawal is associated with increased activity in what four brain areas?
    Nucleus accumbens, amygdala, locus coeruleus, periaquiductal grey
  67. Opiates disrupt __________, and continued use prompts an adaptive mechanism to compensate, during withdrawal this mechanism is still active and overcompensates. What molecule is heavily involved in this mechanism?
    Homeostasis; cAMP
  68. What α2 -adrenergic agonist relieves the chills, tearing, stomach cramps, and sweating associated with opiate withdrawal? Does this do anything for craving?
    Clonidine; NO
  69. Why is methadone somewhat effective for treating opiate addiction?
    Occupies opiate receptor (low occupation for the entire day) reducing severe withdrawal, medically safe, not injected, doesn't produce rewarding rush or euphoria
  70. What form of opiate addiction treatment has an 80% success rate in the first through third years after cessastion?
    Methadone maitenance with counseling
  71. What are two other drugs that are basically longer lasting forms of methadone?
    LAAM and Suboxone
  72. What two drugs prevent the rush of taking heroin or other opiates?
    Naltrexone, nalmefene
  73. What 4 brain regions contain high densities of cannabinoid receptors? What are these area important for?
    • Basal ganglia, cerebellum, hippocampus, cerebral cortex
    • Locomotor activity, coordination, memory
  74. The main cannabinoid receptor is the ___ receptor; this receptor inhibits the release of neurotransmitter by _________, __________, and __________.
    CB1; inhibiting cAMP, inhibiting Ca2+ channels; opening K+ channels
  75. Unlike most receptors the cannabinoid receptor is located on the _________ of the ___________.
    axon terminal; pre-synaptic cell
  76. What selective CB1 antagonist was developed in 1994?
  77. Cannabinoids are rare in that they act as __________; in the brain they inhibit __________ increasing the firing rate of ____________.
    Retrograde messangers; GABA release; pyramidal cells
  78. Two common endocannabinoids are _________ and ___________ these two molecules are derived from _____________ and metabolized by ___________.
    Anandamide; 2-arachidonylglycerol; arachidonic acid; fatty acid amide hydrolase
  79. In general cannabinoids impair learning, however, activation of the CB1 receptor has been implicated in a what specific type of learning?
    Reversal learning (switching strategies)
  80. T/F Use of marijuana and other cannabinoids is not reinforcing in the same way use of other drugs is
  81. T/F Like opiates use of cannabinoids is reinforced by the dopamine system as well as by a poorly understood mechanism most likely involving the opiate system.