Exam 2 Flashcards
what are the benefits of animal testing?
ability to control everything (diet, stress)
face validity
tests done on animals that closely resemble those done to humans
predictive validity
drug effects that are found in the lab mimic or predict the clinical effect
construct validity
the extent to which the animal measurement tool actually measures the characteristic being investigated
vehicle solution
what the drug/placebo is delivered in (saline)
negative control
placebo drug
positive control
drug
fixed ratio
an animal receives a treat after a certain number of presses on a lever
fixed interval
an animal receives a treat after a certain amount of time
what are some measures of motor activity?
video tracking, infrared light beams, open field tests
what are some measures of analgesia?
tail flick test, hot plate test, operant analgesia test
operant conditioning
an animal responds to a cue to obtain a reinforcer (food) and avoid a punishment
what are some learning/memory tests?
t maze, radial arm maze, morris water maze
delayed response test
wechsler memory scale
what are some tests to measure anxiety?
light dark crossing task, elevated plus maze, zero maze, one chamber social interaction test, novelty suppressed feeding paradigm
what are some tests to measure fear
conditioned emotional response, fear potentiated startle
what are some tests to measure depression
behavioral despair, forced swim test, suspension test, chronic mild unpredictable stress model, chronic social defeat stress, maternal separation, sucrose preference test
what are some methods of drug reward and reinforcement
self administration method, conditioned place preference
what are the nine types of stereotaxic surgery
lesioning: an electrode is inserted to destroy brain tissue, and behavior is evaluated before and after
neurotoxins: injected via a cannula to destroy cells
cannulas: can be used to administer drugs or neurotransmitters to stimulate cells
specific neurotoxins: used for different neural pathways that use particular neurotransmitters
microdialysis: measurement of neurotransmitters released in a specific brain region while the subject is engaged in behavior
in vivo voltammetry: implanted microelectrodes measure neurochemicals in extracellular fluid of freely moving animals
implanted macroelectrodes: electrical stimulation produces effects similar to neurotransmitter injection
microelectrodes: can be implanted into a single cell or into the extracellular fluid near a single cell
patch clamp electrophysiology: study of individual ion channels
soup method
isolates and grinds tissue samples to form a homogenate
slice method
use intact piece or slice or tissue for visualization
radioligand binding
amount of bound ligand reflects the number of receptors in the tissue
what is the criteria to determine if ligand is binding to a specific receptor?
specificity, saturability, reversibility, high affinity, biological relevance
autoradiography
radioligand is added to a tissue slice and shows distribution of receptors in the brain
in vivo receptor binding
animal is injected with radioligand while alive
Immunocytochemistry
specific cell localization
western blot
whole tissue
radioimmunoassay
brain region localization
enzyme linked immunosorbent assay
whole tissue
in situ hybridization
locates cells expressing a specific mRNA
DNA microarrays
measure expression of thousands of genes at the same time
Genome wide association studies
uses gene chips consisting of large sets of single nucleotide polymorphisms to search for alleles associated with a disease or disorder
knockout mice
lack gene for making a particular protein
knockin mice
inserted gene is modified to produce a slightly different protein
transgenic mice
one gene has been substituted for another
CRISPR
a faster way to genetically engineer mice
Optogenetics
uses light and microbial opsins to exert precise control over genetically specified cells
chemogenetics (DREADD)
a genetically engineered receptor is inserted into specific brain cells, then activated or suppressed by a ligand that was created to specifically bind to the inserted receptor and nothing else
what are the 10 classes of drugs in the DSM 5
alcohol, caffeine, cannabis, hallucinogens, inhalants, opiods, sedative hypnotic and anxiolytic drugs, stimulants, tobacco
substance use disorders
cognitive, behavioral, and physiological symptoms indicating that the individual continues using the substance despite significant substance related problems
substance induced disorders
reversible substance specific syndrome due to recent ingestion of a substance
oral or transdermal drug administration
relatively slow absorption, slow availability to the brain
IV or inhalation drug administration
rapid drug entry into the brain and a fast onset of drug action, shorter duration of action
positive reinforcers
consuming the drug strengthens whatever preceding behavior was performed by organisms
drug reward
the high
how is drug reinforcement studied
self administration tests
progressive ratio procedure
animals are trained continuous reinforcement schedule, then switched to a low FR schedule, increasing until the animal stops responding
progression of drug use
recreational use -> escalation -> compulsive/problematic use -> withdrawl -> relapse
heritability of substance use disorders
40-60 percent
comorbidity
diagnosis of anxiety, mood, or personality disorder in addition to substance use disorder
self medication hypothesis
individuals suffering from elevated anxiety should prefer sedative drugs, depressed individuals should want stimulant drugs
shared etiology
certain factors contribute to elevated risk of addiction and other psychiatric disorders
reward circuit
area of brain that mediates the acute rewarding and reinforcing effects of most recreational drugs
catecholamines
dopamine, norepinephrine, epinephrine
rate limiting enzyme
tyrosine hydroxylase
how can catecholamine synthesis be increased
administering tyrosine or L-DOPA
What is the multistep pathway of catecholamine synthesis?
Tyrosine hydroxylase -> L DOPA -> AADC -> dopamine -> DBH -> norepinephrine
What loads catecholamines into synaptic vesicles?
VMAT
What blocks VMAT?
reserpine (irreversible) causing a drop in dopamine and norepineprhine, sedation and depression
dopamine release is inhibited by?
autoreceptors
single spiking mode
action potentials appear at irregular intervals (tonic release)
burst mode
a TON of action potentials all at once
catecholamine reuptake
dopamine and norepinephrine transporters return the transmitters to the releasing cell to be broken down or repackaged
how are catecholamine levels regulated
metabolizing enzyme
mesolimbic dopamine pathway
VTA to limbic system (A10)
mesocortical dopamine pathway
VTA to cerebral cortex (A10)
nigrostriatal tract
axons ascend to the dorsal striatum in the forebrain (A9)
5 main subtypes of dopamine receptors
D1 (D1 and D5) and D2 (D2, D3, D4)
What do D1 receptors do?
stimulate adenylyl cyclase
What do D2 receptors do?
inhibit adenylyl cyclase
b1 and b2 receptors
stimulate adenylyl cyclase
a2 receptors
inhibit adenylyl cyclase, inhibits norepinephrine release or cell firing
a1 receptors
activates phosphoinositide
what do sedation and stress have to do with a2 and a1
there is a fine balance between a2 (sedation) and a1 (stress). optimal working memory performance is right in the middle
what are the different forms of cocaine and how are they administered?
coca leaves - chewed with lime or ash
cocaine paste- smoked with tobacco
cocaine salt- snorted or injected
cocaine free base- add water and mix with base (smoke)
crack- smoke
what are most of cocaine’s actions due to
its ability to block reuptake of dopamine, norepinephrine, and 5HT by inhibiting their membrane transporters
what plays the most important role in mediating behavioral responses to psychostimulant drugs?
Dopamine
what are d1 receptors required for
locomotor stimulating effects
Do D1 or D2 knockout mice self administer cocaine
D2 (and D3)
what is the main mode of action of cocaine?
blocks reuptake of DA
where is dopamine produced?
substantia nigra, ventral tegmental area, hypothalamus
where is norepinephrine produced?
locus coeruleus
