Drugs and Behaviour, Chapter 1-7

week 1 (1-39) week 2 (40-53) week 3 (54-73) week 4 (74- week 5 ( week 6 (

Drug

A drug is any substance that alters the physiology of the body but is not a food or a nutrient

chemical name

the terminology refers to the drug composition and where different molecules are combined

generic name

often combines part of the chemical name and may also use a stem to indicate the class or function of the drug

trade name

companies use these generic substances and ™ them through a patent

note: each drug formulation may be different despite having the same active ingredient

preclinical testing

synthesized by researchers. can be in vitro or vivo

phase 1: pharmacokinetic and safety testing

• between 20-100 healthy volunteers are paid to participate in determining investigational drug’s absorption, distribution, metabolism, and elimination from the body

phase 2: small-scale effectiveness testing

• between 100-300 patient volunteers

• closely supervised

• drug’s effectiveness and possible adverse effects

phase 3: large scale effectiveness testing

• 1000-3000 patients

• long term drug use

• university-teaching hospitals using the 3-group design

• allows for widespread sale of the drug

phase 4: postmarketing studies

• available for prescription

• must continue postmarketing surveillance

how are drug doses described

described of their concentration in the body, reported as mg of drug per kg of body weight

ED50 (median effective dose)

• drug of a dose at which 50% of individuals demonstrate the drug effect being measured

• may also refer to the dose at which a single individual exhibits an equivalent to 50% that of the maximum effect the drug will produce at any dose

LD50 (median lethal dose)

dose at which the drug proves lethal in 50% of individuals tested

Therapeutic index (TI)

• drug safety profile

• calculated by LD50/ED50

• one with higher TI is the safer drug

When comparing two drug that produce the same effect the drug with the lower ED50 is the more ______ drug

potent

When comparing two drugs with the same effect, the drug with the greater maximum effect is the more _____ drug

effective

antagonism

when one drug diminishes the effect of another drug

additive

if one drug increases the effect of another (if ED50 decreases)

superadditive

effect is greater than simple combining individual effects

primary effect

• what drug is designed to do

• can be whatever you intend to use the drug for

pharmocokinetics

study of how drug moves around the body. involves processes of absorption, distribution, and elimination

absorption

how a drug gets into the blood

distribution

where drug goes in the body

elimination

how the drug is broken down and leaves the body

sites of action

drugs that only work on specific places

subcutaneous

drug is injected just under the skin

intramuscular

drug is injected into a muscle (deltoid or glutes)

intraperitoneal

inject into the peritoneal cavity, which is a sack containing intestines, liver, and spleen

• not typically used in humans

intravenous

• drug is injected into the bloodstream through a vein

• vein must be close to surface (typically inside of elbow)

transdermal administration

• skin absorption - penetrated with lipid soluble substances

• effectiveness - typically quite slow, quicker if there is a break in epidermis such as with a cut or wound

drug’s lipid solubility

can get stored in fat, decreasing ability to reach CNS

distribution

the trapping of ionized drug molecules on one side of a memberane

• the pKa of a drug is the pH at which half its molecules are ionized.

• this can influence where the drug becomes concentrated in the body; becoming trapped in either a more weak or more acid base in the body

• distribution

presence of the blood brain barrier

• provides a fairly solid lipid barrier making non-lipid soluble substances difficult to get through, aside from incomplete or weak areas

• distribution

placental barrier

distribution

similar to bbb

function of passive and transport mechanisms

• distribution

• specialized transport mechanisms exist to allow non-lipid-soluble molecules through using a carrier protein or ion pumps

liver

• functions as chemical factory

• produces enzymes that participate in the biotransformation of drug molecules to yield metabolites that are subsequently excreted from the body

• ex: alcohol use

• elimination

first pass metabolism

• drugs that are administered orally are subject to this

• the transformation of drug molecules by digestive-system enzymes

• drugs administered in other ways do not pass through the liver, therefore resulting in higher concentrations in the body

• elimination

kidneys

• most of the fluid in the blood is released into one end of the nephron (long tube)

• as fluid passes thru, water and nutrients are reabsorbed

• ionized drug molecules and many metabolites are not reabsorbed, and are excreted from the body in urine

• elimination

rate of elimination

the half-life of a drug is a measure of the amount of time required for the body to eliminate half of a given blood level of the drug

therapeutic window

• therapeutic purposes

• aim is to administer a drug so that blood levels are maintained within the ____

• range in which the drug level is high enough to produce a therapeutic effect but low enough so as to diminish undesirable side effects

behaviour pharmacology

study of the effects of drugs on behaviour

link between chlorpromazine and behaviour

• david macht used antipsychotic drugs on rats to avoid an electric shock

• success of ____ led to demand for a synthesis of pharmacology and behavioural techniques

thorazine

• developed in 1952

• an antipsychotic drug that was effective (did not know why it was effective)

• enabled closing of many psychiatric hospitals

• drugs used to integrate back into society

operant analysis of drug effects

• peter dews

• used skinner box to study the effects of pentobarbital on pigeon pecking

• identified the behaviour was affected by schedule of reinforcement

  • frequency of pecking based on the administration of pentobarbital

within-subjects design

participants behaviour is compared across drugged and drug-free states

between-drugs design

drugged participants behaviour is compared that of drug-free participants

experimental control

treatment of participants in control group should be as similar as possible to the treatment of participants in the experimental group

three groups design

• for therapeutic effects

• one group is given the investigational drug

• one group is given a placebo

• one group is given an established frug with known therapeutic effect

classical conditioning

• involuntary reflexive behaviour is brought under the control of a previously neutral stimulus

• pavlov’s dogs

operant conditioning

• voluntary emitted behaviour is shaped by the delivery of response-contingent reinforcement

• skinner box

• positive reinforcement, negative reinforcement, positive punishment, negative punishment

avoidance escape task

animals can be trained to avoid or excape a noxious stimulus, such as electric shock, and some drugs interfere with these abilities

ex: anti-psychotics dont interfere with motor ability, but instead block the motivation to act

dissociation (state dependent learning)

phenomenon whereby events experienced or information learned in a drugged state might not have the ability to control behaviour or be recalled when the organism is in a non-drugged state, and vice-versa

drug discrimination studies

• take advantage of the ability of interoceptive cues to guide an animals operant responding

• response of animals trained to discriminate a drug from saline can provide insight into the biochemical mechanisms responsible for the subjective effects of a drug

mackworth clock test

watching a hand move step by step around a clock, noting when it moves more than one step at a time

measures attention and vigilance

tolerance

the need to increase a dosage for similar effects or a decreased effectiveness of a drug

cross tolerance

tolerance to one drug can affect another drug’s effectiveness

ex: opioids

acute tolerance

• occurs with a single administration

• makes it difficult for one to view their own intoxication

• ex: alcohol

  • subjective effects of alcohol peak before blood level peaks, and then subjective effects begin to drop quicker than alcohol leaves the system

pharmacokinetic tolerance

• drug movement

• tolerance arises from an increase in the rate or ability of the body to metabolize the drug, resulting in fewer drug molecules reaching their sites of action

• due to enzyme induction, which is an increase in the level of an enzyme the body uses to break down the drug

pharmacodynamic tolerance

• drug change

• arises from adjustments made by the body to compensate for an effect caused by the continued presence of a drug

• adjustments are brought about through homeostasis

how does the functioning of the organism affect tolerance?

• tolerance will develop if there is a significance to the organism

• if rats are given amphetamines, which have an anoretic effect, tolerance to this effect will occur if drug is given a presence of food because the body will try to maintain its homeostasis; the opposite occurs in the absence of food

behavioural tolerance

the effects of learning on tolerance

difference between dependance and addiction

d: when withdrawal symptoms occur once substance is stopped

a: the compulsion to seek out and use substance

opponent process theory

• propose that drugs of abuse stimulate an “A” process that creates a pleasant A state, but soon after a compensatory “B” process is evoked that creates an unpleasant B state

• “hair of the dog”

how does classical conditioning affect drug effects?

• conditions surrounding drug administration can create effects of substance without the substance there

• compensatory processes - body’s resistance to the effects of a drug

• drug tolerance

• withdrawal - associations with places or experiences can create withdrawal symptoms in someone who is no longer using

How does operant conditioning affect drug effects?

• drug tolerance - human and animals can learn to tolerate the effects of substance through reinforcement for this tolerance

• experimental example: rats learned to compensate for the change in their appetite (and therefore response rates) and humans learned to compensate for alcohol effects when being provided a reinforcement such as praise and money

what is sensitization?

an increased effect of some aspects of a drug

• also called reverse tolerance

• stereotyped behaviour:

  • invariable, repetitive movements

  • eye blinking, sniffling, etc

what conditions sensitization?

• environment - appears to mirror tolerance but with drug like response rather than drug opposite response

• operant conditioning - reinforcement can increase effects of substances

how is sensitization different from tolereance?

• persistence - a single dose could lead to long last sensitization

• cross sensitization - has been shown to exist

sensitization mechanism

no single neuron causes it, but the mesolimbic dopamine pathway is involved as well as the nigrostriatal dopamine pathway

expectancy and context - placebo effect

• placebos affect up to 75% of the effectiveness of antidepressants and 50% of the effectiveness of pain relievers

• belief that this is because of an expectation mechanism within the brain that is activated when an individual believes a drug is being administered

placebo effect in medical treatment

• "sham surgeries” can be as effective in medical treatment as drugs

• anxiety and expectation also affect medical treatments

• despite high medical potential, placebos are rarely used in medicine

the nocebo effect

• the nocebo effect leads to a negative expectation and adverse side effects

• the nocebo effects are specific to the drugs people believe they are taking

how does a novel environment affect drug effects

research has shown that locomotor stimulation was enhanced in a new environment vs a familiar one, and sensitization to a drug is quicker in a new setting; both potentially leading to higher addiction

how a drug is administered impacts its effects - self administration

a study on rats found that dopamine levels were increased in the brain of rats that pressed a lever to self-administer an injection of cocaine vs rats who were passively injected whenever the other group self-administered the injection

what is a neuron

• neurons are excitable cells that analyze and transmit information

• control behaviour

• glial cells protect the neurons and are metabolic in nature (clean up trash)

what is a synapse

what are the different parts of the nervous system

what is the potential for disruption to a developing nervous system

what are neurotransmitters

how do we image disruptions to the brain due to drugs

structures of neuron

• dendrite - receive messages

• axons - transmit messages

• myelin sheath - protects the axon

• terminal buttons - transfers the messages to the dendrites of the next neuron

resting potential

a neuron’s activity depends on the breakdowns of the resting potential