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42 Cards in this Set
- Front
- Back
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Experimental Investigation of Drug Effects
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- Independent, Dependent variables
-IV= drug dose; investigate range of doses from low to high to produce a DRC -DV=measure of behavior of subject; drug effect=measured change in behaviour under influence of drug |
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Types of Designs
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-there are 2
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1. Within-subject
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- subject serves as their own control group (compared against themselves)
-use when behavior is stable over days -compare behavior when under influence of drug to behavior when not under influence of drug -all individuals experience all experimental conditions |
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2. Between-subject
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-use when dependent measure is not stable from day to day
-randomly assign rats to different groups -each group is exposed to a different experimental condition |
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Differences between these 2 designs
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- between-subject requires a larger number of subjects because difference between groups is more readily influenced by individual differences
-within-subject design requires fewer subjects but takes longer to carry out |
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Placebo Control
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-control condition: eliminate possibility that method of administration is producing the behavior change rather than the drug
-similar as possible to the drug condition but no drug -typically an injection of the vehicle (ex: saline) in which the drug is dissolved |
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Placebo Effect
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-placebo control conditions differentiate between placebo and drug effects
-placebo is an inert substance that causes no physiological change (ex: sugar pill) -if a person believes that they are getting a drug that will have a particular effect, they will frequently report experiencing the effect even when the drug did not cause it |
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Balanced Placebo Design
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-2x2 experimental protocol designed to manipulate expectations
-2 requirements: subjects must expect or not expect to receive a drug and presence of drug must not be easily detected in the solution given to subjects |
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Marlatt, Demming, Reid (1973) study
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-expectations manipulated: one group told experiment comparing taste of different vodkas, other group told experiment comparing taste of different tonic waters; both groups instructed on how to rate the taste of a drink, given a form, told could consume as much as needed to make comparisons
-solutions received were manipulated: 1/2 subjects in each group received vodka solution, other 1/2 received tonic water; vokda solution: 1pt vodka to 5pts tonic water (vodka not very detectable); two sealed full vodka bottles brought before the subjects expecting to receive vodka, one contained tonic water; 2 sealed full tonic water bottles brought before subjects expecting to receive tonic water, one contained vodka solution; measured the amount of each solution consumed in groups of alcoholics and social drinkers -results: amount consumed were a function of their expectations, not actual substances consumed; alcoholics expecting to receive tonic water by actually got alcohol did not drink more solution than alcoholics |
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Experimenter Bias
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-experimenter may unknowingly influence the results if he/she knows who has been given a placebo and who has been given the drug
-double blind procedure: neither subjects nor researchers know who has been given drug and who has been given placebo |
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Nonexperimental Research
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-is a measure of 2 variables and use statistics to see if there is a relationship between variance in one variable and variance in the other (correlation)
-ex: smoking by mother and infant mortality -problem: must always consider a third variable, cannot say cause |
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Behavior: when dependent measures are used to study drugs?
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- 2 dependent measures used to study drugs
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1. Self Report
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-unstructured verbal descriptions of how person feels under influence of a drug
-structured questionnaires/scales designed to measure how a drug makes a person feel or assess a drug effect (ex: POMS=Profile of Mood States, rate 65 mood related adjectives on a 5pt scale in response to the question "How are you feeling right now?") |
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2. Arousal Level
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-EEG used to measure states of arousal- (a) Albert (EEG=Beta waves), (b) relaxed with eyes closed (EEG=Alpha waves)
-sleep- (a) Alpha, Theta, Delta (Non REM), (b) REM sleep (Cholinergic drugs, antidepressants alter REM sleep; duration and frequency of bouts) |
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Performance Measures in Humans
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-3 performance measures in humans
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1. Perception
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- absolute threshold: lowest level of stimulation (visual, auditory, tactile) that can be reliably detected
-difference threshold: smallest unit of difference in stimulation that can be reliably detected (JND=just noticeable difference) -if we increase threshold (less sensitive); decrease threshold (more sensitive) -CFF (critical frequency fusion): frequency at which a flickering light appears to be constantly illuminated |
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2. Cognitive Performance
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=ability to process, retrieve, store information
-tests of vigilance and attention: (a) visual vigilance test: scan screen for 20mins for stimulus that appears at random locations at random intervals for 2s -tests of memory/learning: (a) digit span: read sequences of digits (1 per sec); repeat digits; if correct, increase next sequence by one digit; if incorrect, decrease next sequence by one digit (digit span= number of digits repeated correctly 50% of the time) |
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3. Motor Performance
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-measures reaction time, tapping rate, hand steadiness, body sway, eye-hand coordination
-finger tapping test: tap index finger as rapidly as possible on a small lever -body sway (Romberg Sway Test): stand erect, feet together, body rigid; index of balance and ability to stand still without swaying or losing balance -pursuit rotor: hold the end of a stylus on a point on a rotating disk -driving: driving simulators in lab or closed courses; assess effects of drugs on ability to operate a vehicle |
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Performance measures in animals
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-2 performance measures in animals
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1. Unconditioned behavior
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-measure behavior (locomotion, eating,drinking)
-SMA (spontaneous motor activity): place an animal in an open field box and count the number of line crossings within a fixed period of time -alternative: grid of infrared beams in cage activates a counter when beams are broken- (a) stereotypy: repetitive movements (rearing or head bobbing) in a vertical dimension (high doses of AMPH), (b)ambulatory movements: produce successive interuptions of consecutive beams (low doses of AMPH) |
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2. Conditioned behavior
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-respondent (Classical/Pavlovian) conditioning:respondent behavior- reflexive, involuntary, elicited; CR: heart rate, GSR (electrical conductivity across skin), salivation, drug effect (opposite)- (a) UCS=UCR, (b) CS+UCS=UCR, (c)CS=UCR (CR)
-operant behavior: voluntary, emitted- (a) consequences influence probability of occurrence of behavior, (b) reinforcement: consequence strengthens behavior -schedules of reinforcement: different schedules produce different patterns of motivated behavior: (a) FR produces "break and run", (b) FI produces "scalloping", (c) VI and VR produce steady/high rates of responding -punishment: consequence weakens behavior |
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Rate Dependency
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- effect of the drug on behavior depends on the rate of occurrence of the behavior under baseline (no drug) conditions
-ex: AMPH (1mg/kg) decreases high occurring behavior and increases low and moderate occurring behavior |
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Rate Dependency on a FI Schedule
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-filled date points=rate of responding as time elapses on an FI 60s schedule
-unfilled data points=effect of cocaine (16mg/kg); increases low rates at the beginning; decreases high rates at the end |
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Tests of Anxolytic Effects (alleviate anxiety)
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-4 tests
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1. Escape-Avoidance Task
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-procedure: turn light on for 30s then shock occurs
-avoidance response: if animal presses lever during 30s when light is on, then shock does not occur -escape response: if animal does not press the lever during the 30s the light it on, they experience the shock, shock can be terminated by pressing the lever -light predicts shock-elicits fear/anxiety -procedure used for assessing anxiolytic effect of drugs |
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2. Light-dark Crossing Test
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- 2 compartments in box, one side is brightly lit and the other side is dark
-rats have preference to be on the dark side -animal placed in the light side; record the number of crossings between the 2 sides, amount of time spent in bright side, total motor activity -anxiolytics increase these measures |
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3. Elevated Plus Maze
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- a cross shaped maze with 2 open arms and 2 enclosed arms; elevated 50cm above the floor
-based on unconditioned aversion to heights and open spaces -measure amount of time spent on open arms -anxiolytics increase this measure, spend more time on open arms when under the influence of this drug |
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4. Geller-Seifter Procedure
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- classic conflict test (Approach-avoidance situation: want to do something but want to avoid it at the same time)
-3 phases: schedule of food presentation for responding, time out, schedule for food and shock presentation for responding (light or tone signals the presence of the punishment contingency) -Benzodiazepine drugs (anti-anxiety) produce a release of punished responding -interpretation: things are not always straight forward and you have to be able to accept other possibilities. perhaps it's having...we need to make sure it's not... (a) a motor activation effect, (b) an increase in the pain threshold, (c) an increase in motivation for food, (d) a memory deficit (BZ at high doses do produce memory deficits) - none of these are supported. It appears to decrease aversiveness of the shock |
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Tests of Analgesic Effect (alleviate pain)
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-2 tests
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1. Tail Flick Test
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-beam of light projected onto an ink blackened spot on a rat's tail, place it over a light source
-measure latency between beam onset and removal of the tail from the light (because it experiences a discomfort) -we would expect that Analgesic increases latency |
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2. Hot Plate Test
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-animal placed on a cylinder on a metal plate maintained at a constant temperature (55 degrees C)
-initial responses: sit on hind paws and lick forepaws -measure latency to paw lick, kicking of hind paw or attempt to escape the apparatus -we would expect that analgesic increases latency |
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Tests of Learning and Memory
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-2 tests
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1. Mazes
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-Multiple T-maze: series of choice points (go left, go right) between start and goal boxes; count number of errors (number of turns>minimum to reach goal)
-Simple T Maze: consists of a single choice (go right, go left) -Radial Arm Maze: multiple arms radiate from central point, small pieces of food at end of each arm in a recessed well. Error: visit an arm already visited; optimal performance: visit each arm only once. different variation: all arms baited; 1/2 arms baited, 1/2 not, use cues within the maze (intramaze) or cues outside the maze with a spatial relation to the baited arms (extramaze)-> Ex: scopolamine: blocks Ach receptors increases errors (increased visits to arms already visited) |
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2. Delayed Matching to Sample
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-present a sample stimulus
-delay (vary to increase memory load; difficulty) -present 2 stimuli; one previously seen; (a)matching sample task: reinforcement is choose stimulus previously seen, (b) non matching sample task: reinforcement if choose stimulus not previously seen |
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Stimulus Properties of Drugs
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-"self report paradigm": animal indicated how it feels (subjective) under influence of drug
-2 levers to press (A&B); in some sessions presses on lever A are reinforcers; in other sessions presses on lever B are reinforced -on days when rat is injected with drug, presses on A, not B, are reinforced; on days when rat is injected with saline, presses on B, not A, are reinforced -use internal state as cue for which lever to press -inject animal with a different drug; if animal presses lever A, then the 2 drugs are experienced similarly by the rat |
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Animal Models- used to study the various types of drugs on certain disorders
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-3 types
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1. Homologous
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-model resembles the disease in most aspects and shares a common etiology
-ex: experimentally-induced poliomyelitis |
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2. Isomorphic
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-model resembles the disease, but differs in etiology
-Ex: experimental Parkinson's |
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3. Predictive
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-model does not resemble the disease in symptoms or etiology, useful for predicting therapeutic value of agents used to treat the disease
-Ex: behavioral tests (catalepsy) used to test clinical potency for anti-psychotics |
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Drug Development
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-2 phases
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1. Preclincial Testing
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-extensive animal research- test for effective doses, behavioral effects, side effects
-determine toxicity, lethal dose, teratogens -effects of long term chronic use -absorption, metabolism, binding, pharmacological profile -conducted on rodents, sometimes primates |
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2. Clinal Trials
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-Phase 1: in healthy humans, establish safety and dose ranges, side effects
-Phase 2: statistical evaluation-compare control/experimental groups in double blind placebo control design -Phase 3: extend clinical evaluation, drug made available to investigators in hospitals and universities, in 2002 pharmaceutical companies required to register all clinical trials using a drug (prevents doing multiple studies and only publishing one with significant results that occurred due to chance), FDA or Health Canada approval (approved for use with humans [most drugs never reach this stage], costs approx. $800mil to get a drug to the marketing phase -Phase 4: accumulation of data on the success of the drug as used in the clinic, develop improved dosing schedule and report all cases of adverse reactions |
