Drugs Brain and Mind - Chapter 2

tail-flick test

measures response of the animal to heat applied to the tail

hot plate test

latency to respond to a thermal stimulus applied to paws » time it takes the mouse to lick the hind paw, vocalize, or jump from surface

analgesia

reduction of perceived pain without loss of consciousness

radial arm maze (RAM)

hungry rat allowed to explore, food bait at end of each arm

learn to visit each arm only once on a given day

• must remember which arms were visited previously

• external visual cues as guides

• sensitive to hippocampal lesions

morris water maze

opaque circular pool of water, external visual cues as guides

sensitive to hippocampal lesions

barnes maze

external visual cues as guides

no swimming involved (unnatural behavior for rodents)

delayed response test

food is placed in selected well, covered and revealed, animal must choose the correct well

working memory, sensitive to PFC lesions

anxiety test: open field, elevated plus maze, elevated zero maze, light/dark

a natural conflict situation occurs when a rodent is exposed to an unfamiliar environment

anxiolytic drugs increase these behaviors, anxiogenic drugs decrease these behaviors:

• time in center of open field

• time spent in open arms of mazes

• time spent in light

pre-pulse inhibition (PPI)

schizophrenia and ASD patients exhibit impaired PPI

impairments in sensorimotor gating: ability to distinguish between stimuli and filter out uneccesary inputs

• inappropriate thoughts, hallucinations, sensory experiences, etc

inter cranial self-stimulation (ICSS)

animal self-administers a weak electric current to brain reward areas

threshold: current value at which animal continually self-administers

conditioned place preference (CPP)

conditioned association between drug effect and environment

drug discrimination testing

animal learns to discriminate between drug and saline based on internal cues produced by the drug

optogenetics

insertion of genes into neurons that confer light responsiveness to control events within these neurons

used in freely behaving animalsi

implanted microelectrodes

implanted into a single cell (intracellular recording) OR

into the extracellular fluid near a single cell (extracellular recording)

in vivo microdialysis

measure neurotransmitter release in specific brain region while subject is actively engaged in a behavior

“soup” method (quantification)

tissue sample is isolated and ground (homogenate)

number of receptors in brain region and affinity for drugs

“slice” methods (spatial localization)

uses intact slice of tissue

visualize distribution of receptors in the brain

positron emission tomography (PET)

maps distribution of radioactively labeled substance, used to determine location of drugs

locates areas of brain activity when person is performing cognitive tasks

functional MRI (fMRI)

oxygenated hemoglobin has a different magnetic resonance signal than oxygen-depleted hemoglobin

active brain cells need more O₂ » blood flow increases

transgenic mice

human genes inserted into mice

models for neurodegenerative diseases

knockout mice

lack gene for making a particular protein

constitutive (germ-line), site-specific (ire-lox) or inducible (tet on/off)

knock-in mice

point mutations target a single nucleotide to produce a single a.a. substitution

may produce loss or gain of function

study of a specific mutation

knockdown mice

RNAi mice

allows assessment of lowered levels of gene product

might be more valid representation of the human condition than KO