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PS263 - Ch 15 Textbook.docx

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Wilfrid Laurier University
Todd Ferretti

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. th  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
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