CH4 Flashcards
Behavioural measures are crucial for understanding the ________ basis of behaviour, and drug-induced changes in that behaviour. Developing ______ _____ of psychiatric disorders, and screening newly designed drugs in _______ and ______ pharmaceutical settings
neurochemical, animal models, preclinical, clinical
used with animals and and humans to measure specific physiological, emotional, cognitive, or other psychological processes
test/assay
used to test spatial memory
water maze
used to test for anxiety
elevated plus maze
used to test for rewards
conditioned placed preference
Ideally, tests should tap into similar ______ in humans. However, you can never truly know what an animal is _____, and must infer changes in psychological states based on changes in _______. Typically, multiple tests and ____ procedures are needed to partition complex behaviours into component processes
functions, thinking, behaviour, control
entail some manipulation that causes some cellular/functional change that resembles what is observed in the disease
models
manipulation in models may mimic _______ occurring in the disease (e.g. genetic, environmental), or may be ______ (pharmacological), but still induces a similar behaviour phenotype. For more complex psychiatric disorder, it is near impossible for one model to recapitulate all aspects of the disorder and multiple models are used to re-create different ______.
pathophysiology, artificial, symptoms
seeing what causes the certain symptoms rather than the whole disorder
research domain criteria
surgical brain lesions that permit comparison about the function of a brain area
stereotaxic surgery
broad sucking up of the cortex that permanently destroys tissue
aspiration
the irreversible frying of neurons, which destroys the axon as well as cell bodies
radiofrequency
use of glutamate agonists that overexcites and selectively kills intrinsic neurons in the brain regions; does not affect axons connected to other regions; irreversible
excitotoxic lesion
intracranial infusion of a drug via a cannula to suppress neural activity by use of anaesthetics, or GABA agonists
reversible lesions / inactivation
Intracranial infusions similar to reversible lesions may be used to infuse _____ into specific brain regions to examine where a drug may act to affect ______. It only affects certain nuclei at a time to see what region is being affected
drug, behaviour
NT specific _____ can be used to identify the role of the NT in a particular behaviour. The toxin is injected directly into the______, which is taken to the ______ and destroys them. Cell bodies that do not use the specific transmitters are ____ affected
neurotoxin nucleus, terminals, not
DA, NE neurotoxin
6-hydroxydopamine (6-OHDA)
5-HT neurotoxin
5.7-dihydroxytryptamine
electrical stimulation that produces action potentials and NT release; can be used to assess whether activation of a nucleus induces certain patterns of behaviour; usually a complementary technique to lesions
implanted microelectrodes
measures NTs released in a specific region while the subject is engaged in behaviour
microdialysis
in microdialysis, artificial _____ is pumped in through a probe implanted at precise sites in brain tissue. _____ enter the solution in the probe via diffusion. Tiny amount of fluid are pumped out of the probe and analyzed by techniques such as ________. The sample rate is _____ minutes.
CSF, NTs, high performance liquid chromatography, 1-2
used with microdialysis to separate the sample into components depending on the molecular size or ionic charge
high performance liquid chromatography (HPLC)
can determine the concentration of molecules of interest
electrochemistry
When a glass tip is placed in front of the membrane and suction is applied to create a small tear so that the membrane wraps around the electrode tip
intracellular patch clamp
intracellular patch clamps allows recording of ______ _____, and changes in ____ ______ (ion flux). it provides detailed information of how drugs affect _______ ________ or ionic currents that regulate neural activity. It is measured in ____/____/_____. To use, the animal must be ____ or an in ____ brain slice preparation must be used
membrane potentials, electrical currents, synaptic transmission, mV, V, Amps, anaesthetized, vitro
When a glass or metal electrode is placed near a neuron and only action potentials are recorded
extracellular microelectrodes
With extracellular recordings, _____ cells can be recorded from at once, and this can be done in ______/_____ animals to assess changes in cell firing associated with behaviour.
multiple, awake, behaving
when a tissue sample is isolated and ground into a homogenate for analysis; often used to quantify the amount of receptors and if there are receptors there
soup methods
uses intact piece/slices of tissue to localize targets in the brain
slice method
ligands embedded in a radioactive atom (e.g. hydrogen) which can be used to index receptor binding by the amount of radioactivity in the sample, or through special photography; not the most selective
radioligands
created by injecting an antigen (e.g. receptor) into a host animal and collecting blood samples. Antibodies are tagged with coloured chemicals or fluorescent dues for visualization; harder to create, not always available
antibodies
proteins that bind to specifically targeted proteins
antibodies
When a solution containing a tissue homogenate or generic cells transfected with specific receptor is incubated with radioligand
radioligand binding
In radioligand binding, cells expressing the receptor of interest are _______ in a solution containing the radioligand. After a _____, unbound radioligand is removed and the remaining amount that is bound to the tissue is measured. It reflects the ______ of receptors in the tissue. You can use this method to identify receptors in a particular brain region by dissecting out that brain region and _______ it
bathed, washout, number, grinding
radioligand binding is also used to identify if a novel drug has some ___/_____ for a particular receptor. Only cells expressing the receptor of interest are used. A standard radioligand is combined with a _____ _____ (not radioligand), and displacement of the standard ligand at different _____ of the test are used as indexes. A wash out is needed to test how much more the test compounds ____ to the receptor. If you need a ____ concentration of test compound to bump off the standard radioligand, it is binding with stronger affinity. You can also test a drug’s affinity for different receptor ________.
affinity/selectivity, test compound, doses, stick, lower, subtypes
_____ assays can be used to look at changes in ______ activity (e.g. concentration of DA on ______ receptor stimulation, and inhibition of ______) by applying different concentrations of a drug to cells to obtain a _____ function, if there is no change in ______ of receptor at different doses of ligand while also sticking to it, it is an _____
agonist, enzymatic, D2, cAMP, dose-response, 2nd messenger, antagonist
To measure enzyme activity in _____ receptors, radioligand bind must be used, while ______ (____) measures can be used for ionotropic receptors, to assess how the drug activates ionic currents mediated by the receptor. Additionally, NTs can be used in conjunction with an ______ to measure electrical change produced by it
metabotropic, electrophysiology, patch clamp, allosteric modulator
When a radioligand is incubated with tissue slices, then exposed to film sensitive to radioactivity; used to visualize receptor distribution and requires highly selective drug
receptor autoradiography