PS263: Chapter 15 – Drug Addiction & the Brain’s Reward Circuit
Pharmacological: Pertaining to the scientific study of drugs & principles.
Basic Principles of Drug Action
Psychoactive Drugs: Drugs that influence subjective experience & behaviour by
acting on the nervous system.
1. Oral Ingestion: Preferred; once swallowed they dissolve fast in stomach fluids which
carry them to the intestine & into the bloodstream. Some drugs readily pass through
the barrier & not intestine – broken into metabolites; breakdown products of the
body’s chemical reaction
a. Advantage: Easy & relatively safe, Disadvantage: Unpredictable
2. Injection: The effects are strong, fast & predictable; made subcutaneously (SC) into
the fatty tissue just beneath skin, intramuscularly (IM) into the large muscles, or
intravenously (IV) directly into veins just beneath skin.
a. Prefer IV because it goes directly to brain, the speed & directness are not
able to be counteracted = overdose, allergy, impure dose
b. Effects - Develop scar tissue, infections, and collapsed veins.
3. Inhalation: Absorbed through bloodstream through capillaries in lungs, anesthetics
administered this way; smoking. Hard to regulate & lung damage
4. Absorption through Mucous Membrane: Through the nose, mouth & rectum (I.e.,
cocaine is administered through nasal membranes with no damage)
Once a drug enters the bloodstream it is carried to the blood vessels of the CNS; the
blood-brain barrier makes it hard for dangerous chemicals to pass.
Some drugs act on neural membranes through CNS (alcohol) while others bind to a
particular synapse receptors, influence synthesis, transport, etc.
Drug Metabolism: Actions of most drugs are terminated by enzymes synthesized by
the liver; these enzymes stimulate the conversion of active drugs to non-active
forms; eliminates ability to pass through lipid membrane.
Drug Tolerance: State of decreased sensitivity to a drug that develops as a result of
exposure to it – A shift in the dose-response curve: 1) in tolerant individuals the
same dose has less effect, 2) A greater dose is required to produce the same effect.
1. 1 drug can produce tolerance to other drugs by same mechanism: cross tolerance
2. Tolerance often develops to some effect but not others; tolerance to one effect, or
increasing sensitivity to a drug is called drug sensitization.
3. Tolerance is not unitary phenomenon – no single underlying mechanism for all.
Metabolic Tolerance: Drug tolerance that results from changes that reduces the
amount of drug getting to its sites of action.
Functional Tolerance: Drug tolerance that results from changes that reduce the
reactivity of the sites of action (tolerance to psychoactive drugs)
Withdrawal Syndrome: After significant amounts of a drug have been in the body for
a period of time, its sudden elimination can trigger an adverse physiological reaction
o Effects are virtually always opposite to the initial effects of the drug
o Individuals who suffer withdrawal reactions are physically dependent.
Exposure to a drug produces compensatory changes in the nervous system that
offset the drug’s effect & produce tolerance – when eliminated from the body these
compensatory changes (w/ no drugs) manifest themselves as withdrawal symptoms
Addicts: Habitual drug users who continue to use a drug despite its adverse effects
on their health & social life & despite repeated efforts to stop using the drug,
Role of Learning in Drug Tolerance
Contingent Drug Tolerance: Refers to the demonstrations that tolerance develops
only to drug effects that are actually experienced, most use before & after design: PS263: Chapter 15 – Drug Addiction & the Brain’s Reward Circuit
Before-and-after Design: 2 groups of subjects receive the same series of drug
injections & the same series of tests, but the subjects of 1 group receive the drug
before each test while the others receive it after – at the end the subjects receive the
same dose; compares the degree to which the drug disrupts test performance
Conditioned Drug Tolerance: Refers to demonstrations that tolerance effects are
maximally expressed only when a drug is administered in the same situation in
which it has previously been administered.
o Situational Specificity of drug tolerance: large, reliable & general effect
Siegel Addicts may be susceptible to the lethal effects of a drug OD when the drug
is administered in a new context; the addict becomes tolerance when they
repeatedly self-administer their drug in the same environment, they take larger
doses to counteract the diminution of drug effects – if the addict administers the
usual dose in an unusual situation, tolerance effects are not present to counteract.
o Each incidence as a Pavlovian conditioning trial in which various
environmental stimuli that usually predict are conditioned stimuli.
Conditioned Compensatory Responses: As the stimuli repeatedly predict the
effects of a drug come to elicit greater & greater conditioned compensatory
responses, they increasingly counteract unconditional effects of the drug & produce
situationally specific stimuli.
Most demonstrations of conditioned drug tolerance have employed exteroceptive
stimuli (external, public, such as drug-administration environment) as the
conditioned stimuli. Interoceptive stimuli (internal, private stimuli) are effective.
Ramsay & Woods The unconditioned stimulus is the disruption of neural
functioning that has been directly produced by the drug & the unconditioned responses
are the various neutrally mediated compensatory reactions to unconditioned stimulus.
Five Commonly Abused Drugs
1. Tobacco: When a cigarette is smoked nicotine (major psychoactive ingredient) &
4,000 other chemicals; tar – are absorbed through the lungs while nicotine acts on
nicotinic cholinergic receptors in the brain. Leading preventable cause of death.
a. 400,000 premature deaths per year, 1 in 5 deaths in the U.S.A.
Nonsmokers often result with nausea, vomiting, dizziness, flushed, diarrhea, etc.
while smokers report they are more relaxed, alert, and less hungry after smoking.
Compulsive drug craving is readily apparent in habitual smokers - those who stop
smoking experience withdrawal: depression, anxiety, restless, irritable, etc.
o 70% who experiment with it, become addicted
Smoker’s Syndrome: Characterized by chest pain, labored breathing, wheezing,
coughing & heightened susceptibility to infections of the respiratory tract.
Chronic smoker’s = pneumonia, bronchitis, emphysema & lung cancer – increases
cancer of the larynx, mouth, esophagus, kidneys, pancreas, bladder & stomach.
o Greater risk in developing CV disorders; claim they smoke to relieve tension
when in reality it causes more tension (between smokes) also: panic attacks
Buerger’s Disease: In 15 of 100,000 individuals, mostly male smokers where the
blood vessels especially in the legs become restricted
Those who live with smoker’s develop heart disease & cancer; nicotine is a
teratogen (agent that can disturb the normal development of the fetus)
Smoking during pregnancy increases likelihood of miscarriage, stillbirth & early
death of a child
Many people stop smoking when they experience the health benefits, however
nicotine patches & etc. have proven to be only marginally effective. PS263: Chapter 15 – Drug Addiction & the Brain’s Reward Circuit
2. Alcohol: Involved in over 3% of all deaths in the USA (including birth defects, ill
health, accidents & violence) 13 million users and about 80,000 die each year.
a. Alcohol molecules are small & soluble in fat & water in all parts of the body.
b. Intoxication: red facial flush due to dilation of blood vessels in the skin,
increases the amount of heath that is lost from blood to air (hypothermia)
It is a depressant because at moderate-high doses it depresses neural firing, while
at low doses it can stimulate neural firing & facilitate social interaction.
Addiction has major genetic components; heritability of 55% & genes = alcoholism
Moderate: various cognitive, perceptual, verbal & motor impairment, loss of control
High: unconsciousness, BAL = 0.5% could result in death; diuretic: increases urine
Produces tolerance & physical dependence; livers of heavy drinkers metabolize
alcoholic quicker – most tolerance is functional & withdrawal produces headaches,
nausea, vomiting, and tremulousness (hangover) Withdrawal has 3 phases:
1) 5-6hrs after cessation; severe tremors, agitated, headache, nausea, vomiting,
abdominal cramping, profuse sweating & sometimes hallucinations.
2) 15-30hrs after; convulsive activity
3) a day or 2 later; lasts for 3-4 days & is called delirium tremens (DTs) characterized
by hallucinations, delusions, agitation, confusion, hypothermia, tachycardia – lethal.
Alcohol affects almost every tissue in the body, chronic consumption; brain damage.
Korsakoff’s Syndrome: Neuropsychological disorder; memory loss, sensory & motor
dysfunction & sometimes severe dementia by inducing thiamine deficiency & stoke.
Chronic consumption causes extensive scaring/cirrhosis of the liver (major death),
alcohol erodes the heart muscles increasing heart attack, irritates the lining of the
digestive tract increasing oral cancers & ulcers, pancreatitis (inflammation of the
pancreas) and gastritis (inflammation of the stomach) accidents; roads, homes, etc.
Fetal Alcohol Syndrome (FAS): Mothers who consume substantial amounts of
alcohol while pregnant; the child suffers from: brain damage, mental retardation,
poor coordination, poor muscle tone, LBW, retarded growth or deformity.
No cure for alcoholism, Disulfiram (Antabuse) can help reduce consumption under
certain conditions. It interferes with the metabolism of alcohol & produces an
accumulation in the bloodstream of acetaldehyde (breaks down alcohol)
Positive: Moderate drinking reduces the risk of coronary heart disease.
3. Marijuana: Dried leaves & flowers of cannabis sativa (common hemp plant) 2
million Americans have used; typically smoke these leaves in a joint or pipe; also
effective when ingested orally (brownie)
a. Psychoactive effects are attributable to THC but it also contains over 80
cannabinoids (chemicals of the same class as THC) mostly in the resin.
b. Resin can be extracted & dried to form a dark corky material = hashish.
Used to be used for rope, smoking became prevalent in the 20 century and many
misconceptions – it is legally classified as a narcotic in many states & punishment.
Popularization in the 1960s – low doses: “social dose” experiences a sense of well
being, restlessness, alteration of sensory perceptions (senses), hunger, etc.
High Dose: Short-term memory is impaired, ability to carry out tasks with multiple
steps declines, speech is slurred & meaningful conversation is difficult.
Addiction potential is low – only 10% use daily, usua