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
what technique is used to analyze microdialysis samples?
HPLC
26
what does HPLC stand for?
high-performance liquid chromatography
27
how does HPLC work
separates proteins in sample based on size or ionic charge gets concentrations from chromatography picture prodcued
28
techniques using microelectrodes
intracellular/ patch clamp extracellular
29
how does the intracellular/patch clamp work
electrode is stuck into the neuron to measure membrane potential and changes in electrical currents
30
what can we study using intracellular/ patch clamp technique
very detailed info on how drugs are affecting synaptic transmission/ ionic currents in one cell
31
how does the extracellular patch work
electrode stays adjacent to neurons to record action potentials
32
what can we measure using extracellular electrodes technique
change in cell firing and associated behaviour in groups of cells in live animals
33
which type of electrode technique has more detailed recordings of electrical changes in a cell?
intracellular/ patch clamp
34
what techniques in neuropharmacology are receptor measures?
radioligand binding receptor autoradiography immunocyrochemistry enzyme-linked immunosorbent assay (ELISA) in situ hybridization
35
what is the soup method?
where tissue sample is isolated, homogenized, and treated with markers
36
for what type of analysis do we use the soup method?
quantifying amount of target/receptor
37
what is the slice method?
tissue is sliced into intact pieces and exposed to markers
38
what type of analysis do we use the soup method for?
localizing a target/receptor
39
radioligands
ligands embedded with radioactive atom
40
how are antibodies created
inject antigen (receptor) into a host animal who then creates anantibody for it collected in their blood samples
41
which is more specific; radioligands or antibodies? why?
antibodies, specially designed for target radioligands may have affinities for other receptors
42
what are the two ways we can use radioligand binding
in a tissue homogenate in generic cells transfected with specific receptor
43
what can we study using readioligand binding?
receptors in particular region affinity of novel drugs vs the ligand
44
how can we test the affinity of a new drug using radioligand binding
wash solution in both less radioactivity means more novel-drug binding
45
true or false; receptor measures for studying neuropharmacology let us study the location of receptors and function of drugs
False, receptor methods give no information on drug function
46
how can we measure drug efficacy in metabotropic receptors?
measure changes in 2nd messenger enzyme activity at different doses
47
how can we measure drug efficacy in ionotropic receptors?
measure activation of ionic currents caused by receptor with electrophyisiological measures
48
what research methods use the soup?
radioligand binding ELISA
49
what research methods use slices?
receptor autoradiography immunocytochemistry in situ hybridization
50
how does receptor autoradiography work?
brain slices with radioligands exposed to film sensitive to radioactivity
51
how does immunocytochemistry (ICC) work?
brain slices with antibodies show cells with target receptor using coloured labels
52
what can make antiboy binding less selective?
the addition of coloured labels
53
what is more specific; receptor autoradiography or immunocytochemistry?
immunocytochemistry
54
how can we study location and/or distribution of receptors in the brain?
receptor autoradiography immunocytochemistry
55
what method can we use to quantify amounts of receptors in the brain?
ELISA
56
how does ELISA work
antibodies link to enzymes enzymes act on substrate to form coloured product colour intensity proportional to antigen product
57
what does ELISA stand for?
enzyme-linked immunosorbent assay
58
how does in situ hybridization (ISH) work
detects mRNA moleules that synthesize target protein with complimentary RNA fragments
59
advantages of ISH
highly selective easy to analyze comparably extremely sensitive
60
disadvantage of ISH
mRNA found in the cell does not mean the target protein exists functionally in the cell
61
what can we measure using ISH?
how much specific protein production is happening in any given moment which cells may contain the protein
62
brain activity measures
PET fMRI pharmacological MRI EEG
63
what does PET stand for
position emission tomography
64
how does PET work
inject radioactive isotope into subject to identify metabolic energy being used (areas receiving incresed blood flow)
65
what can we study using PET using radioligands?
location/concentration of receptors in living brain NT release by displacement of the radioligand
66
how does fMRI work?
measures BOLD signal
67
what does BOLD stand for
Blood Oxygenation Level Dependent
68
what is BOLD showing us?
oxygented versus deoxygenated blood in areas since they release different magnetic signals
69
true or false; fMRI has much better spatial and temporal resoluton than PET
true
70
pharmacological fMRI
analyzing changes in brain function following drug adminstration
71
temporal resolution of PET
few minutes
72
temporal resolution of fMRI
1 second
73
true or false; bold is an indication of firing activity
false; indication of presynaptic inputs to that region what the brain is hearing
74
what does EEG stand for
Electroencephalography
75
how does EEG work
measure synchronous firing of large groups of neurons by placing electrodes on the scalp
76
what are event related potentials (ERPs)
events that create a specific characteristic of waveform
77
what can we measure using EEG
how ERPs vary in psychiatric populations or with drug use can drugs normalize wavepatterns
78
how does spatial and temporal resolution in EEG compare to other brain activity measures?
EEG has better temporal resolution but more poor spatial resolution
79
what are some disadvantages of EEG
cannot study specific brain areas cannot study subcortical activity cannot pick up on minute differences in activity
80
genetic/brain manipulations techniques
knockouts knockin/trangenes conditional knockout optogenetics
81
knockout
gene for protein is deleted
82
knockin/transgenes
original protein gene is removed and substituted for another
83
what is the issue with simple gene manipulations of knockout/knockin?
develop with removed/subbed gene may lead to compenstion by othergenes therefore masking effect of mutation
84
conditional knockout
knockout only occurs in subset of brain regions
85
what gene manipulatipon techniques can be used to avoid developmental issues of knockout/in
condtional knockout gene inhibition/excitement when drug administered viral vectors
86
what can we study using genetic manipulations?
identify function of proteins
87
how does optogenetics work?
using targetted viral vector, insert gene for light-sensitive ion channel/pump implant optic fibers connected to laser/LED
88
what is the role of channels in optogenetics
will be activated by certain wavelength of light
89
excitatory channel used in optogenetics and its function
channel rhodopsin conducts Na
90
inhibitory channel used in optogenetics and its function
halorhodopsin