Ch. 4 Methods of Research in Psychopharmacology Flashcards

1
Q

advantages of animal studies

A

full control of living conditions, genetic background, etc
research methods that are unethical with human
generalization between human and non human mammals

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2
Q

test definition

A

measure specific physiological, emotional, cognitive etc. processes

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3
Q

example of a test and what it study’s

A

water maze, measures spatial memory

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4
Q

what can we study using tests

A

how a drug may affect a particular behaviour

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5
Q

animal model definition

A

some manipulation in the animal causes some cellular/functinoal change seen in a disease

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6
Q

true or false; animal models tend to focus on a particular observed symptom rather than an entire disease?

A

true

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7
Q

what can we study using animal models

A

difference between healthy and sick population
drugs that alleviate symptoms

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8
Q

two different lesion techniques

A

permanent lesions
reversible lesions

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9
Q

how are permanent lesions made

A

aspiration
radiofrequency
excitotoxic

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10
Q

how do excitotoxins work

A

glutamate agonsists that over-excites and selectively kills neurons in brain region

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11
Q

what is an example of excitotoxins?

A

kainic acid
ibotenic acid

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12
Q

how do reversible lesions work

A

drug infused intracranially suppresses neural activity for a time

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13
Q

what can we study using lesions?

A

function of a specific brain region and how it effects behaviour

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14
Q

what can study using neurotoxins

A

identify role of neurotransmitter in particular behaviour

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15
Q

what do neurotoxins do?

A

targets a type of neurotransmitter and destroys it and the terminal that contains it

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16
Q

neurotoxin that destroys DA and NE

A

6-OHDA

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17
Q

neurotoxin that destroys 5-HT

A

5,7-Dihydroxytryptamine

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18
Q

neurotoxin that destroys Ach

A

192lgG-saporin

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19
Q

how do implanted macroelectrodes work

A

electrical stimulation cause APs and NT release

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20
Q

what can we study using implanted macroelectrodes

A

whether activastion of a neruon region leads to certain patterns of behaviour

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21
Q

what techniques in neuropharmacology are vivo measures

A

microdialysis
intracellular patch/clamp
extracellular

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22
Q

what techniques in neuropharmacology are brain manipulations

A

stereotaxic lesions
neurotoxins

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23
Q

what does microdialysis measure

A

NT release in specific brain region while behaviour is occuring

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24
Q

how does microdialysis work

A

artificial CSF pumped in at precise site
CSF pumped out and molecules in it diffuse into test tube through semi permeable membrane

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25
Q

what technique is used to analyze microdialysis samples?

A

HPLC

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26
Q

what does HPLC stand for?

A

high-performance liquid chromatography

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27
Q

how does HPLC work

A

separates proteins in sample based on size or ionic charge
gets concentrations from chromatography picture prodcued

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28
Q

techniques using microelectrodes

A

intracellular/ patch clamp
extracellular

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29
Q

how does the intracellular/patch clamp work

A

electrode is stuck into the neuron to measure membrane potential and changes in electrical currents

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30
Q

what can we study using intracellular/ patch clamp technique

A

very detailed info on how drugs are affecting synaptic transmission/ ionic currents in one cell

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31
Q

how does the extracellular patch work

A

electrode stays adjacent to neurons to record action potentials

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32
Q

what can we measure using extracellular electrodes technique

A

change in cell firing and associated behaviour in groups of cells in live animals

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33
Q

which type of electrode technique has more detailed recordings of electrical changes in a cell?

A

intracellular/ patch clamp

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34
Q

what techniques in neuropharmacology are receptor measures?

A

radioligand binding
receptor autoradiography
immunocyrochemistry
enzyme-linked immunosorbent assay (ELISA)
in situ hybridization

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35
Q

what is the soup method?

A

where tissue sample is isolated, homogenized, and treated with markers

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36
Q

for what type of analysis do we use the soup method?

A

quantifying amount of target/receptor

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37
Q

what is the slice method?

A

tissue is sliced into intact pieces and exposed to markers

38
Q

what type of analysis do we use the soup method for?

A

localizing a target/receptor

39
Q

radioligands

A

ligands embedded with radioactive atom

40
Q

how are antibodies created

A

inject antigen (receptor) into a host animal who then creates anantibody for it
collected in their blood samples

41
Q

which is more specific; radioligands or antibodies? why?

A

antibodies, specially designed for target
radioligands may have affinities for other receptors

42
Q

what are the two ways we can use radioligand binding

A

in a tissue homogenate
in generic cells transfected with specific receptor

43
Q

what can we study using readioligand binding?

A

receptors in particular region
affinity of novel drugs vs the ligand

44
Q

how can we test the affinity of a new drug using radioligand binding

A

wash solution in both
less radioactivity means more novel-drug binding

45
Q

true or false; receptor measures for studying neuropharmacology let us study the location of receptors and function of drugs

A

False, receptor methods give no information on drug function

46
Q

how can we measure drug efficacy in metabotropic receptors?

A

measure changes in 2nd messenger enzyme activity at different doses

47
Q

how can we measure drug efficacy in ionotropic receptors?

A

measure activation of ionic currents caused by receptor with electrophyisiological measures

48
Q

what research methods use the soup?

A

radioligand binding
ELISA

49
Q

what research methods use slices?

A

receptor autoradiography
immunocytochemistry
in situ hybridization

50
Q

how does receptor autoradiography work?

A

brain slices with radioligands exposed to film sensitive to radioactivity

51
Q

how does immunocytochemistry (ICC) work?

A

brain slices with antibodies show cells with target receptor using coloured labels

52
Q

what can make antiboy binding less selective?

A

the addition of coloured labels

53
Q

what is more specific; receptor autoradiography or immunocytochemistry?

A

immunocytochemistry

54
Q

how can we study location and/or distribution of receptors in the brain?

A

receptor autoradiography
immunocytochemistry

55
Q

what method can we use to quantify amounts of receptors in the brain?

A

ELISA

56
Q

how does ELISA work

A

antibodies link to enzymes
enzymes act on substrate to form coloured product
colour intensity proportional to antigen product

57
Q

what does ELISA stand for?

A

enzyme-linked immunosorbent assay

58
Q

how does in situ hybridization (ISH) work

A

detects mRNA moleules that synthesize target protein with complimentary RNA fragments

59
Q

advantages of ISH

A

highly selective
easy to analyze comparably
extremely sensitive

60
Q

disadvantage of ISH

A

mRNA found in the cell does not mean the target protein exists functionally in the cell

61
Q

what can we measure using ISH?

A

how much specific protein production is happening in any given moment
which cells may contain the protein

62
Q

brain activity measures

A

PET
fMRI
pharmacological MRI
EEG

63
Q

what does PET stand for

A

position emission tomography

64
Q

how does PET work

A

inject radioactive isotope into subject to identify metabolic energy being used (areas receiving incresed blood flow)

65
Q

what can we study using PET using radioligands?

A

location/concentration of receptors in living brain
NT release by displacement of the radioligand

66
Q

how does fMRI work?

A

measures BOLD signal

67
Q

what does BOLD stand for

A

Blood Oxygenation Level Dependent

68
Q

what is BOLD showing us?

A

oxygented versus deoxygenated blood in areas since they release different magnetic signals

69
Q

true or false; fMRI has much better spatial and temporal resoluton than PET

A

true

70
Q

pharmacological fMRI

A

analyzing changes in brain function following drug adminstration

71
Q

temporal resolution of PET

A

few minutes

72
Q

temporal resolution of fMRI

A

1 second

73
Q

true or false; bold is an indication of firing activity

A

false; indication of presynaptic inputs to that region
what the brain is hearing

74
Q

what does EEG stand for

A

Electroencephalography

75
Q

how does EEG work

A

measure synchronous firing of large groups of neurons by placing electrodes on the scalp

76
Q

what are event related potentials (ERPs)

A

events that create a specific characteristic of waveform

77
Q

what can we measure using EEG

A

how ERPs vary in psychiatric populations or with drug use
can drugs normalize wavepatterns

78
Q

how does spatial and temporal resolution in EEG compare to other brain activity measures?

A

EEG has better temporal resolution but more poor spatial resolution

79
Q

what are some disadvantages of EEG

A

cannot study specific brain areas
cannot study subcortical activity
cannot pick up on minute differences in activity

80
Q

genetic/brain manipulations techniques

A

knockouts
knockin/trangenes
conditional knockout
optogenetics

81
Q

knockout

A

gene for protein is deleted

82
Q

knockin/transgenes

A

original protein gene is removed and substituted for another

83
Q

what is the issue with simple gene manipulations of knockout/knockin?

A

develop with removed/subbed gene may lead to compenstion by othergenes therefore masking effect of mutation

84
Q

conditional knockout

A

knockout only occurs in subset of brain regions

85
Q

what gene manipulatipon techniques can be used to avoid developmental issues of knockout/in

A

condtional knockout
gene inhibition/excitement when drug administered
viral vectors

86
Q

what can we study using genetic manipulations?

A

identify function of proteins

87
Q

how does optogenetics work?

A

using targetted viral vector, insert gene for light-sensitive ion channel/pump
implant optic fibers connected to laser/LED

88
Q

what is the role of channels in optogenetics

A

will be activated by certain wavelength of light

89
Q

excitatory channel used in optogenetics and its function

A

channel rhodopsin
conducts Na

90
Q

inhibitory channel used in optogenetics and its function

A

halorhodopsin