Midterm 1 Flashcards
What is the EC50? How do you find it on a graph?
The dose that is effective in 50% of the time, assuming everyone is the same. Found at Y=50
Think: effective
What is the KD50?
The dose that proves lethal 50% of the time
Think: kill dose
What is the ED50?
Similar to the EC50, but considering variability
Think: effective dose
What is the LD50?
Similar to KD50, but considering variability
Think: lethal dose
What is the therapeutic index? How is it calulated?
The ratio of dose required for a desirable effect to undesirable effect
TI=LD50/ED50
TI=KD50/EC50
What is potency? How can you gauge it on a graph?
The extent of the drug’s effects
More potent = leftmost on graph
What is drug efficacy? How can you gauge it on a graph?
A drug’s ability to produce a maximum, biologically functional response
Higher curve = more effective
What are primary effects? Secondary effects?
Primary: the intended reason for taking the drug
Secondary: side effects, anything else
Give an example of a polar ion
Therosine
Name some charged ions
Arginine+, Histidine+
Name some hydrophobic ions
Valine, Isoleucine, Leucine, Methionine, Tryptophan, phenylalanine
Name some special case ions
Cystine, glycine, proline
What type of bond is the strongest? Weakest?
Strong: Covalent bond
Weak: Hydrophobic bond
Explain lipid diffusion
The migration of lipophilic and non-charged ions through the cell membrane. Guided by concentration gradients
Explain aqueous diffusion
Pores allow the passage of specific sized molecules through tight junctions
NOT through blood-brain barrier
Explain the relation between pH and PKA
PKA is the pH at which 50% of ions are charged
Charged drugs cannot pass barrier
How can you predict the charge of an ion from pH and PKA?
PKA>pH = weak base is neutral
PKA<pH = weak base is ionic (charged)
What is PKA?
The pH at which 50% of the molecules are charged
Explain active transport
Specific molecules bind to specific carriers to be transported over the barrier
What is saturated active transport? Inhibited?
Transport that requires no energy
Blocked transport
Explain endo/exocytosis
Passing over (in or out) the membrane, surrounds the molecule in a vesicle
What is ADME?
Absorption, Distribution, Metabolism, Excretion
What is bioavailability?
how much of the drug ‘makes it in’ or takes effect on the body
What are the different routes of administration?
Parenteral: Injection, Inhalation, Transdermal, Nasal, Topical
Enteral: Oral, rectal
What are the types of injections? (6)
Sub-q: under skin
Intramuscular: muscle
Intraperitoneal: peritoneal cavity
Intravenous: vein
Intrathecal: between skull and V1
Intracerebroventricular: brain ventricles
How do injections get absorbed into the body?
Injection makes its way into bloodstream
Makes its way in deoxygenated blood through heart to lungs
Oxygenated and sent back through heart to body to brain
How are inhaled substances ADME?
Substance inhaled into lungs(A)
Gas exchange allows drug to pass into oxygenated blood, pumped through heart to brain and body (D)
Slow metabolism throughout body (M)
Expelled by breathing out (E)
THC ADME when inhaled
Inhaled particles remain in lung and absorb into bloodstream for distribution (A,D)
Body metabolizes and expels like solids (M,E)
How are oral substances ADM?
Absorption through the walls of the stomach and intestine (A)
Into bloodstream via villus, pass throughout body (D)
Breakdown in saliva, stomach acid, liver, kidneys (M)
What is first pass metabolism?
Any drug absorbed via the digestive system is pre-metabolized in the stomach, gut, and liver
How are transdermal substances absorbed?
Lipophilic substances seep in through S.C (top layer of skin)
What are distribution compartments?
How do they affect distribution
Fat, bone, intracellular fluid, extracellular fluid
Fat and bone have reservoirs that hold on to substances (slower release)
Where does most of metabolism occur?
Liver and Kidneys
Explain phase 1 metabolism
Give examples of the enzymes
Enzymes break down the molecule to make them polar
CYP1, CYP2, CYP3, CYP3A4
Explain phase 2 metabolism
Drugs are transformed into conjugates
How do the kidneys aid in metabolism?
Filers certain substances out of blood, sends waste to be eliminated
What are first-order kinetics?
The elimination rate of substances dependent on concentration
What is half-life when discussing elminination?
Half life is the time it takes for the body to eliminate 50% of the substance
What is zero-order kinetics?
When a substance is eliminated at a constant rate, independent of concentration
What is the therapeutic window?
the range of a substance’s concentration in the blood between maximum and minimum efficacy
How can you determine the therapeutic window?
The same as the therapeutic index
KD50/EC50
LD50/ED50
What factors affect PK/PD?
Genetics, age, sex, state of subject, diet
Explain how the state of a subject affects PK/PD
Alcoholics create more of the enzyme (alcohol dehydrogenase) for breakdown, thus it is faster
Explain how age can affect PK/PD
Children and fetuses do not produce alcohol dehydrogenase enzyme, cannot break down
What is an agonist effect?
How does it relate to drugs?
A molecule that activates the receptor it binds to
An drug that produces an agonist effect will activate the receptor, but does not stop when overstimulated
What is an antagonist effect?
How does it relate to drugs?
A molecule that blocks the receptor it binds to
A drug that is an antagonist will block a ligand from activating the receptor
What is a full agonist effect?
The maximum activation response to molecule binding
What is a partial agonist effect?
Activates to mid potential, above average but not full
What is a competitive antagonist?
When a molecule will compete for the receptor
What is an irreversible antagonist?
A molecule that kicks everything else off the receptor to block it
What is an inverse agonist effect?
How does this relate to drugs?
When a GPCR spontaneously activates due to an absence of ligands
A drug that takes this effect will reverse that spontaneous activation
What is an allosteric modulator?
A substance that binds to additional receptors, altering the effect of primary binding
What is PAM? What does it mean
Positive allosteric modulator
A substance that enhances the primary effect
What is NAM? What does it mean
Negative allosteric modulator
A substance that inhibits/reduces the primary effect
What is a 1+1=0 drug interaction? Give an example
An antagonist effect, drug B cancels/reduces drug A
Naloxone for opiods
What is a 1+1=2 drug interaction?
An additive effect, drug B adds to the effect of drug A
What is a 1+1=3 drug interaction?
A superadditive / synergism effect, the combined effect of A with B are greater than the effect of A and B (A+B) > (a) + (b)
What is a 0+1=2 drug interaction?
A potentiation effect, drug A has no effect unless taken with drug B
How is resting potential maintained?
Simple diffusion, electrostatic charge, differential permeability, transporter pumps
How does simple diffusion maintain resting potential?
Na+, K+, Cl-, A- move along their concentration gradient, in and out of the cell to maintain an inner difference of -70mV
How does electrostatic charge maintain resting potential?
K+, Na+ are repelled by the more positive charge outside the cell, inclined to stay internal
Cl-, A- are repelled by the more negative charge inside the cell, inclined to stay external
How does differential potentiation maintain resting potential?
Non-gated ion channels are open to allow K+ and Na+ to pass as needed
How do transporter pumps maintain resting potential?
Active exchange of K+ (in) for Na+ (out)
Sodium-potassium pump
How is an action potential generated (7 steps)
- Threshold met
- Na+ enter
- K+ leaves
- Na+ channels close
- K+ keeps leaving (repolar - hyperpolarization)
- K+ channels close causing (cell is hyperpolar)
- Excess external K+ diffuses away
What is an EPSP? Explain it
Excitatory Post Synaptic Potential
Causes an excitation response, starts a process
What is an IPSP? Explain it
Inhibitory Post Synaptic Potential
Causes an inhibition response, stops something
How does an ionotropic receptor work?
Charged ions (Na+, K+, Cl-) bind to the receptor to activate or inhibit
What are the products of ionotropic receptors?
IPSP or EPSP
How does a metabotropic receptor work?
G-protein coupled molecules bind to the receptor and initiate a second messenger
What are the second messengers associated with metabotropic receptors?
cAMP
cGMP
What does the second messenger cAMP do?
cGMP?
Activates PKA
Activates PKG
Proteins (enzymes) that alter the functioning of other receptors
What is Glutamate?
How is it synthesized? Reuptake/Breakdown?
Role?
Excitatory amino acid
Synthesized from glutamine
Reuptake via EAAT
Role: cell plasticity, learning + memory
What is the AMPA?
How does it work?
Glutamate receptor
Ionotropic
Glutamate/drug binds
Na+ IN, K+ OUT
Local depolarization and at Mg2 site
EPSP
What is NMDA?
How does it work?
Glutamate receptor
Binding
Depolarizing opens Mg2 site
Glutamate and glycine receptors bind
Na+, Ca2+ INTO cell
What receptor does PCP affect? How?
NMDA
Antagonist effect
What is GABA?
How is it synthesized? Reuptake/Breakdown?
Role?
Inhibitory amino acid
Synthesized by GAD from glutamate
Reuptake by GAT
Role: memory, impulse, decision making
What is GABA(A)?
How does it work?
GABA receptor
Ionotropic
Substance binds, Cl- passes into cell
IPSP
What receptor does Alcohol affect?
How?
GABA(A)
Binds to receptor, opening flow of Cl- into cell
Inhibits actions
Affects: memory formation, decision making, impulse control
What is Dopamine?
How is it synthesized? Reuptake/Breakdown?
Role?
Monoamine
Synthesized from Tyrosine
Reuptake by DAT
Breakdown by MAO, COMT
Role: reward-related processes, motor behaviour
What is the D1?
How does it work
Dopamine receptor
Metabotropic
Binding activates the G protein
Stimulate cAMP (second messenger) production
Increase excitability
What is the D2?
How does it work?
Dopamine receptor
Metabotropic
Binding activates the G protein
Inhibit cAMP (second messenger) production
Decrease excitability
What effect does Cocaine have?
How?
Agonist effect on dopamine
Blocks DAT reuptake, causing dopamine to keep binding and overstimulate cell
What effect do methamphetamines have?
How?
Agonist effect on dopamine
Reuptake reversal
Mimics dopamine and binds to D receptors
Excess dopamine binds after
Overstimulate cell
Affects: euphoria in reward path
What is serotonin?
How is it synthesized? Reuptake/Breakdown?
Role?
Monoamine
Synthesized from Tryptophan
Reuptake by SERT
Breakdown by MAO
Role: mood, sleep/wake cycles, aggression
What kind of receptors are the 5-HT?
Serotonin receptors
5-HT1,2,4-7 = Metabotropic
5-HT3 = ionotropic
What effect does LSD have?
How?
Agonist effect on serotonin
LSD binds to receptors, inhibiting or exciting them
Affects: ability to sleep, mood
What effect does Ecstasy have?
How?
Agonist effect on serotonin
Mimics serotonin to bind first,
excess serotonin then binds and over stimulates cell
Affects: mood, sleep, perception, appetite
What is Acetylcholine?
How is it synthesized? Reuptake/Breakdown?
Role?
Monoamine
Found at neuromuscular junction, PNS, CNS
Synthesized from acetate+choline
Breakdown by enzyme acetylcholinesterase
What is the nAChR?
How does it work?
Nicotinic ACh receptor
Ionotropic
ACh/drug binds to receptor
Na+ IN, K+ OUT
EPSP
What effect does nicotine have?
How?
nAChR agonist effect
Binds to receptors like ACh
What is the mAChR?
How does it work?
Muscarinic ACh receptor
Metabotropic
ACh binding to M1,3,5 = second messenger to open K+ and Cl- channels
ACh binding to M2,4 = second messenger to decrease cAMP
What effect does muscarine have?
Atropine?
mAChR agonist effect
mAChR antagonist effect
What are endocannabinoids?
How is it synthesized? Reuptake/Breakdown?
Role?
Neuromodulator
Produced from lipid compounds
Breakdown by enzymes
Role: homeostasis
What is the CBR1?
How does it work?
Endocannabinoid receptor
Metabotropic
Inhibits pre-synaptic action by Depolarization induced Suppression of inhibition/excitation
Binds to pre-syn. heteroceptors, G-protein inhibits Ca2+ channel
What effect does marijuana have?
How?
Agonist effect on dopamine
THC binds to heteroreceptors, blocking feedback to dopamine production
Dopamine continues to bind
Affects: wakefulness, pain receptors, appetite, memory + concentration
What are some types of opioid peptides?
How are they synthesized? Reuptake/Breakdown?
Role?
Beta-endorphin, enkephalin, dynorphin
Synthesized by polypeptides
Breakdown by peptidases enzyme
Role: homeostasis, reward-related processes, stress+pain response
What are the MOR/KOR/DOR?
How do they work?
Opioid peptide receptors
Metabotropic
G-protein regulates K+, Ca2+, or second messenger
Inhibits excitability
What effect does morphine have?
Naloxone?
Agonist effect on MOR receptor
Antagonist effect on MOR receptor
What effect does heroin have?
How?
Agonist effect on MOR
Binding turns off dopamine inhibition
Affects: pain receptors, stress response, emotional attachment
What is norepinephrine (NE)?
Role?
Monoamine
Role: attention, sleep/wakefulness. feeding behaviours, emotion, arousal, motivation
What are Alpha1, Beta1, Beta2?
How do they work
NE receptors
Metabotropic
Excitatory
What is Alpha2?
How does it work?
NE receptor
Autoreceptor
Inhibitory
What is the division of the nervous system?
NS
1. Central
2. Peripheral
a) Somatic
b) Autonomic
- Parasympathetic
- Sympathetic
What does the somatic NS in charge of?
Motor and sensory nerves
What is the autonomic NS in charge of?
Stress response
What part of the NS is most affected by drugs?
Autonomic NS
What is the parasympathetic NS in charge of?
Rest/Digest
What is the sympathetic NS in charge of?
Fight/Flight/Freeze
What does the Medulla Oblongata play a role in?
Consciousness, heart rate, blood pressure, breathing, muscle tone, reflexes
What drugs affect the Medulla Oblongata?
In what way?
Barbiturates, opioids, alcohol: depress breathing
Opiates, nicotine: cause nausea + vomiting
What does the Pons play a role in?
Bridges and refines motor commands conveyed between parts of the cortex and cerebellum
What drugs affect the Pons?
In what way?
Benzodiazepines: increase the inhibitory effects of GABA, relieving anxiety
Amphetamines, cocaine: stimulate adrenergic synapses, causing anxiety
What does the cerebellum play a role in?
Receives and processes sensory and motor stimuli
Maintains posture, fine-tunes movement, smooths eye movement, procedural memory
What drugs affect the cerebellum?
In what way?
Alcohol may affect this area and cause motor effects
What are the two subsets of the Reticular formation?
What differentiates them?
Ascending (RAS) - to brain
Descending - to spinal cord / body
What does the Descending Reticular Formation play a role in?
Autonomic nervous system, reflexes, posture balance, motor movement
What does the Ascending Reticular Formation play a role in?
Cortex activation, cognitive arousal, selective attention, wakefulness
What drugs affect the Reticular Formation?
In what way?
Barbiturates, alcohol: decrease the ability of the neurons in RAS to fire repeatedly, causing a decrease in arousal
What is the PAG?
What role does it play a part in?
Periaqueductal Grey
Pain sensation, defensive behaviour
What drugs affect the PAG?
In what way?
Opioids: block pain by stimulating the PAG
What is the VTA?
What role does it play a part in?
Ventral Tegmental Area
Component of the reward pathway, sends dopamine throughout the brain
What does the Basal Ganglia play a role in?
Voluntary movement, action selection, switching between motor beh/habits/eye movement, memory for locations in space, classical conditioning
What are the components of the Basal Ganglia?
GPe
GPi
SNr
SNc
STN
What drugs affect the Basal Ganglia?
In what way?
L-Dopa: can alleviate parkinson’s symptoms
Antipsychotics: can cause them
What does the limbic system play a role in?
Emotion, memory, alertness, stress response, executive function, motivation
What are some of the main parts of the limbic system?
Hippocampus, Amygdala, Thalamus, parts of the Cortex, hypothalamus
What is the role of the hippocampus?
How does it interact with drugs?
Learning, declarative + spatial memory
Mediates place/drug preference
What is the role of the amygdala?
Process neg. emotions (FEAR/RAGE), emotional memory, behavioural memory
What does the Thalamus play a role in?
Transmit sensory input to cerebral cortex, regulate arousal + excitability of cortex
What does the Hypothalamus play a role in?
Homeostasis control: body temp, blood pressure, fluid balance, metabolism, eating/drinking motivation, etc
What drugs affect the Hypothalamus? How?
Benzodiazepines reduce aggression and produce a calming effect
What parts of the Cortex play a role in integrating sensory information?
Primary Visual/Auditory/Somatosensory cortices
What are secondary and association cortices? What are their roles?
Smaller, non-primary
Integrate sensory information with other sensory perceptions and store them as memories
What does the Primary Motor Cortex play a role in?
Voluntary motor actions
What does the Prefrontal Cortex play a role in?
Sending and receiving information from the limbic system
Abstract reasoning, insight, planning, motivation, decision making, judgement
What drugs affect the Prefrontal cortex? How?
Alcohol inhibits many decision making and impulse control mechanisms
What is the Nigrostriatal pathway? What NT travels through it? What path does it take?
Pathway for movement
Dopamine
Substantia Nigra to Striatum
What is the Mesolimbic pathway? What NT travels through it? What path does it take?
Reward pathway
Dopamine
Ventral Tegmental Area to Nucleus Accumbends
What is the Mesocortical pathway? What NT travels through it? What path does it take?
Pathway for motivation and emotion
Dopamine
Ventral Tegmental Area to Cortex
What is the Tuberoinfundibular pathway? What NT travels through it? What path does it take?
Posterior pituitary pathway
Dopamine
Hypothalamus to Pituitary
What is the path of the Norepinephrine pathway?
What role does it play a part in?
FUN FACT
From the Locus Coeruleus throughout the brain
Arousal and motivation
Locus Coeruleus is BLUE
What pathway includes the Basal Nucleus of Mynert and Medial Septal Area? In what way?
The Acetylcholine pathway
Plays part in learning, memory, and cortical action
What disease impacts the Acetylcholine pathway? How?
A loss of ACh transmission results in Alzheimer’s Disease
What pathway includes the Mesopontine tegmental area? In what way?
The Acetylcholine Pathway
Role: REM sleep
What role does the VTA play in the Acetylcholine pathway?
Reward system
What is the 5-HT pathway? What is its role?
The 7 different Raphe Nuclei project information to the CNS in ascending/descending motion
Role: Controls enkephalin release (PAIN)
How can teratogens alter development?
What defines HOW it will affect a fetus?
Teratogens can interrupt the formation of circuits and prematurely prune connections
Time is the most indicative of what effect will occur
Explain MRI
What is the final outcome?
Magnetic Resonance Imaging
Relies on magnets and radio waves to map the movement of hydrogen atoms
Results on a high contrast resolution image
Used to look at the body
Explain fMRI
How does it differ from MRI?
Functional MRI
Uses blood-oxygen level to measure brain activity
Used to look at the brain rather than the body
Explain PET scans
What are they used for?
PET uses radioactive tracer isotopes to capture metabolic/biochem function
Relies on O2, N, C, F-
Allows the study of receptor distribution/density, metabolic activity and changes in receptors over time
Provide a brief summary of the history of Behavioural Pharmacology
1920s: Psychopharmacology, Macht at Johns Hopkins, still used outside North America
1950s: Beh. Pharma, Dews at Harvard, Operant analysis of drug effects
Today: Beh. Pharma, Drug effects tested using Beh. Psych + Beh. Neuroscience
In the early 1900s, who’s theory changed how Psychology did testing?
How?
What is the logic?
Watson’s behaviourism proposed that Psych needs precise, systematic means of describing, recording, and analyzing beh.
Observable behaviour is objective
Explain the Forced Swim Test
Why is it used?
What drug-related research does it aid with? How?
A mouse/rat is placed in a beaker of water, the amount of time spent swimming is recorded
Good predictive validity
Useful for Antidepressant testing: reduced immobility in non-depressed animals indicates a functional drug
Explain the Avoidant-Escape Task
What conditioning does it rely on?
Animal learns that the tone indicates an incoming shock, decision to leave is rewarded
Operant conditioning
What is a controlled experiment?
An experiment in which it would be possible to say, with a degree of certainty, what would happen if a drug is NOT given
Use of control group
What is experimenter bias? How is it countered?
The unconscious change of outcomes due to the experimenter’s beliefs, reactions, wording, etc
Countered using blind experiments
What are the features of a parallel design experiment?
Between subjects
Compares control group to drug group
Random selection
What are the features of a crossover design experiment?
Within subject and between subject
Compares individuals with and without drug
Compares Group A to Group B
Washout period: time taken to rid body of substance
What are the features of a balanced placebo design experiment?
When is it used?
G1: expects drug, gets drug (drug effect only)
G2: Expects drug, gets placebo (placebo effect)
G3: expects placebo, gets drug (placebo+drug)
G4: expects placebo, gets placebo (baseline)
Mainly used in the mid 1970s
What are the features of a 3-group design experiment?
G1: Placebo
G2: Drug
G3: Control / established drug
What are some features of a Longitudinal study?
Limitations?
Non experimental
Long, expensive, big sample
Follows individuals over time
Attrition (quitting), ‘Survivor bias’
What are some features of a cross sectional study?
Quick less expensive
Snapshot view in time
Compares groups at different stages at one point in time
Generalizability
Show patterns of change
What are some features of a prospective study?
individuals followed over time to see final outcome - not yet known
Less risk of spurious correlations
Increased cost, time, effort
What are some features of a cohort study?
Observe sample over time, looking for the development of a specific response
Less risk of spurious correlations
What are some features of a case control study?
Compare specific cases to control
Increased risk of spurious correlations (case selection bias)
What are some features of a retrospective study?
Outcomes already known, working back to find correlations
Increased risk of spurious correlations
What does direction refer to in a correlation?
If the correlation is positive or negative
What scale is used to determine strength?
What are the levels?
Schober
0.00 to <0.10 = negligeable
0.10 to <0.40 = weak
0.40 to <0.70 = moderate
0.70 to <0.90 = strong
0.90 to 1.00 = very strong
Explain the spontaneous motor activity test
How does it relate to drug testing?
Animal placed in open field, movement activity measured electronically or by line-crossing
Time spent in middle indicates low anxiety
Study effects of benzodiazepines (anti-anxiety)
What tests can be used to measure unconditioned behaviour?
Spontaneous motor activity test
Elevated Plus Maze
Explain the elevated plus maze
How does it relate to drug testing?
Cross shape, two closed in arms, two open
Time spent in open arms indicates low anxiety
Study effects of benzodiazepines (anti-anxiety)
What is classical conditioning?
Give an example
The continued pairing of a CS and US to produce a reflex (UR)
Eventually CS produces UR (now CR)
Bell + food = salivate
Bell = salivate
Explain the conditioned place preference test
How does it relate to drug testing?
US: drug
UR: reaction to drug
CS: coconut smell
CR: go to coconut smell
Time spent in coconut chamber determines addictiveness / strength of reinforcement
What are some features of Drug Discrimination testing
How does it work?
Used to test the onset and duration of subjective effects
To determine receptors being binded
Substitution tests for like-drugs
Operant or Classical conditioning
What are the features of a Fixed Interval schedule of reinforcement?
How does it affect response rate?
“Every so often”
Reinforcement is only given after a set amount of time following task
Moderate response rate, significant pause after reinforcement
What are the features of a Variable Interval schedule of reinforcement?
How does it affect response rate?
“Value dependent”
Reinforcers are given at different intervals, making it impossible to predict
Slower response rate
What are the features of a Fixed Ratio schedule of reinforcement?
How does it affect response rate?
“Response Quota”
Animal must perform the task a given number of times for reinforcer
High response rate
What are the features of a Variable Ratio schedule of reinforcement?
How does it affect response rate?
“Estimated Quota”
Animal must perform the task about X many times
High response rate
What do Self Administration Studies measure?
How do drugs impact the rate of responding?
Compares the pressing of a drug-paired and a saline-paired lever
Uses a fixed or progressive ratio schedule
Preferential increase of pressing drug lever indicates the drug is a strong reinforcer, may press more often even if not getting drug
What do ICSS studies measure?
How do drugs impact the rate of responding?
Measure of a drug’s ability to alter operant responding to electrical stimulation of reward path
The addition of a drug lowers the Hz needed to reach the response threshold - facilitates responding (sensitive to)
What do Choice Studies measure? How do they work?
How do drugs affect the rate of responding?
Measure of choice between a drug and another reinforcer (drug b/food/etc)
Animal gets equal exposure to lone-reinforcers, then must choose which they want
Choice indicates the stronger reinforcer
How are subjective effects measured in people?
Explain each test
Introspection: ask how they feel
Rating scales + Self-reports: rate their experiences in different factions, ask about specific feelings
How are objective effects measured in people?
Drug state discrimination
Perception
Motor performance
Attention + Vigilance
Memory
Response inhibition
Driving ability
How do drug state discrimination tests measure objective effects?
Participant is exposed to IDENTIFIED drug and placebo
They are then asked to identify an UNIDENTIFIED drug as similar effect to drug or placebo
How do perception tests measure objective effects?
Explain the different tests
Measure the sharpness of senses (sight and hearing)
Critical flicker fusion frequency: measure of the ability to detect a flicker in the light
Auditory flicker
How do motor performance tests measure objective effects?
Explain the different tests
Measure the reaction time in motor related activities
Simple RT test: press button ASAP after cue
Complex RT test: multiple responses and cues
Pursuit rotor: Hand-eye coordination
Finger tapping rate
Hand steadiness
How do attention and vigilance tests measure objective effects?
Explain the tests
Measure of response time to visual cues
Mackworth clock test: press button when clock moves by 2sec instead of 1sec
How do memory tests measure objective effects?
Explain the tests
Measure of recall
Short term
N-back test: when cue symbol is shown, must recall the last N# back (previous symbols)
Long term
Free recall: remember a list of words to be recalled later
Cued recall: remember a list of words to pick out from a longer list later
How do response inhibition tests measure objective effects?
Explain the tests
measure the ability to stop or withhold reaction
Go-No go: Press on cue 1, don’t press on cue 2
Go-Stop: like go-no go but with STOP cue. STOP cue closely follows other cues, must halt initial reaction
What drugs will affect response inhibition? How?
Alcohol: increase the delay between cue and STOP required for accurate response
How do driving-ability tests measure objective effects?
Explain the tests
Measure of perception, motor control, attention, response
In traffic
In closed course
Simulated
What is tolerance?
The effect of repeated drug exposure that results in diminished effects or the need to increase doses to reach intoxication
What is cross-tolerance?
Increased tolerance of one drug will affect all the drugs in the family
What is acute tolerance?
How does it explain tolerance?
Short term tolerance
The point at which a higher concentration makes no difference in effect
Receptors are desensitized and cannot be re-activated for a given time
What is Pharmacokinetic tolerance?
How does it explain tolerance?
Give an example
The increase in the rate/ability of the body to metabolize a drug
*ADME
Fewer molecules at the site of action change the duration of action
Heavy drinkers produce more enzymes to break down alcohol
What is Pharmacodynamic tolerance?
How does it explain tolerance?
Adjustments made by the body to compensate for effects caused by the continued presence of a drug\
Homeostasis
The body gets better at compensating over time and can handle the drug better
What are the two ways in which Pharmacodynamic tolerance results in changes
Up-regulation: added receptors increase sensitivity
Down-regulation: blocked receptors reduce stimulation and sensitivity
What is behavioural tolerance?
Learned tolerance
Through experience with a drug, an organism can learn to decrease the effect
How to sober up
What is the Opponent Process Theory?
The theory that the stimulation of drugs activates two processes that work oppositely to create dependence
Explain the steps of the Opponent Process Theory
Drug is administered, starting A process
A effect is pleasurable
As drug wears off, so does A effect, starting B process
B effect is dysphoric/negative
Explain how to classically condition a drug effect using an example
US: drug
UR: Nausea
CS: cues presented prior to drug
CR: person starts to get nauseous after the cues are presented, no drug
Explain how to classically condition a compensatory effect using an example
US: drug
UR: Pain relief
CS: cues presented prior to drug
CR: person starts feeling pain relief after cues, no drug
What is conditional tolerance?
How can it be dangerous
What is another name for it?
Increased tolerance that is tied to the environment the drug is typically administered in
If the drug is taken in a novel location, the person is at higher risk for OD
Environmental sensitization
How can operant conditioning lead to behavioural tolerance?
Use an example
G1: Amph, task with DRL- low response rate reinforcement (must wait a given time between responses)
G2: Task with DRL, Amph
If G2 is given the Amph first, they never learned to withhold their responses and do so too early (punished)
What is sensitization?
What part of the cell does it affect?
The increase in drug effects as a result of repeated administrations
Can affect the pre and postsynaptic neurons
What is the nocebo effect?
When you expect negative outcomes and therefor experience negative outcomes
How does self administration affect drug effects?
The control of self-administration increases dopamine production and amplifies the effect
How do novel environments affect drug effects?
In novel environments, the locomotion stimulation is increased (hyperlocomotion)
