Ch 15 Drug Addiction & the Brain’s Reward Circuits

1. Ch 15 Drug Addiction & the Brain’s Reward Circuits

2. Drug Administration & Absorption • Psychoactive drugs: • Drugs that influence subjective experience & behavior by acting on the nervous system • Drugs usually administered: • Oral ingestion • Injection • Inhalation • Absorption through mucus membranes • Method of administration affects the rate & degree of impact

3. Drug Administration & Absorption • Oral Ingestion: • Once swallowed, dissolves in the stomach & absorbed into the bloodstream in the intestine • Some drugs pass through the stomach lining & act faster (ex: alcohol) • Unpredictable; strength of effect can depend on fullness • Injection: • Common medical technique • Strong, fast & predictable • Ideal for doctors; potentially dangerous for addicts because there is almost no chance to counteract the effects of overdose or impurity • Can be subcutaneous (into fatty tissue below the skin), intramuscular (into large muscles), or intravenously (directly into vein)

4. Drug Administration & Absorption • Inhalation: • Enter the bloodstream through capillaries in the lungs • Difficult to regulate the dose & when used chronically can damage the lungs • Ex: anesthetics, tobacco, marijuana • Absorption through mucus membranes: • Mucus membranes present in the nose (snorting), mouth & rectum • Ex: cocaine

5. Drugs & CNS • Once a drug enters the bloodstream, it is carried to the blood vessels of the CNS • BBB keeps many drugs out (but obviously not all) • Can act diffusely on neural membranes throughout the CNS or can act specifically by binding to specific receptors, influencing transport, release or deactivation of NTs, or influencing postsynaptic chemical processes • Actions of most drugs are terminated by enzymes in the liver • Convert the drugs to nonactive form: drug metabolism

6. Drug Tolerance • Drug tolerance: decreased sensitivity to a drug that develops over repeat exposure • A given dose of drug has less effect than it did before • Or it takes a larger dose to produce the same effect as before • Cross tolerance: one drug can produce tolerance to other similar drugs • Possible to have tolerance to some effects of a drug but not others • 2 categories of changes with tolerance • Metabolic: reduces the amount of drug getting to the sites of action • Functional: reduces the reactivity of the sites of action • Tolerance to psychoactive drugs • Ex: reduce # of receptors, decrease binding to receptor • Drug sensitization: increased sensitivity to a drug; opposite of tolerance

7. Drug Withdrawal & Physical Dependence • Sudden elimination of a drug after a significant amount has been in the system for awhile can cause adverse physiological reaction: withdrawal syndrome • Individuals who experience withdrawals are said to be physically dependent on that drug • Effects of withdrawal are usually opposite to effects of the drug • Suggests they may be caused by the same neural changes that produce drug tolerance • Exposure to a drug produces compensatory changes in the nervous system that offset the drug’s effects & create tolerance

8. Addiction • Addicts: Habitual drug users who continue to use a drug despite its adverse effects on their health & life & despite repeated efforts to stop • Addiction is not merely a function of physical dependence • Because even after withdrawal symptoms have passed, they often keep using the drug/relapse • Drugs are obviously not the only thing that people can become addicted to • Other addictions may be based on the same neural mechanisms

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10. 5 Commonly Abused Drugs • Tobacco • Alcohol • Marijuana • Cocaine (and other stimulants) • Opiates (heroin & morphine)

11. Tobacco • The major psychoactive ingredient of tobacco is nicotine • Acts on cholinergic receptors in the brain • Nicotine and over 4,000 other chemicals, referred to as tar, are absorbed through the lungs when a cigarette is smoked • The leading preventable cause of death in Western countries • About 1 in 5 deaths in the US • Highly addictive (within a few weeks), compulsive drug cravings, quick & intense withdrawals • About 70% of people who try smoking become addicted • Major genetic component to nicotine addiction

12. Tobacco • Smoker’s syndrome: consequences of long-term tobacco use; chest pain, difficulty breathing, wheezing, coughing & increased susceptibility to respiratory infections • Chronic smokers are highly susceptible to many potentially lethal lung disorders (pneumonia, bronchitis, emphysema & lung cancer) • And other cancers: larynx, mouth, esophagus, kidneys, pancreas, bladder & stomach • Increased likelihood of cardiovascular disease

13. Tobacco • Smokers are actually more tense; smoking only seems to relax them • More prone to panic attacks • Tobacco smoke can also have negative effects on those around a smoker • Nicotine is a teratogen (agent that can disrupt normal development of the fetus) • Treatments for nicotine addicts are only marginally effective, but many people do stop smoking • Those who quit before age 30 live almost as long as non-smokers

15. Alcohol • Alcohol molecules are small and both fat & water soluble so they can invade all parts of the body • Classified as a depressant • Moderate to high doses depress neural firing • However, at low doses it stimulates neural firing (and facilitate social interaction) • Addiction has a major genetic component • Moderate doses result in cognitive, perceptual, verbal & motor impairment, and a general loss of control • High doses cause unconsciousness & even death from respiratory depression (at around 0.5%)

16. Alcohol • Alcohol intoxication often causes facial flushing from dilated blood vessels in the skin, causing the body to lose heat • Is also a diuretic (increases production of urine) • Alcohol withdrawal: headache, nausea, vomiting, tremors • Severe withdrawals: 3 phases • 5-6 hours after: severe tremors, agitation, headache, nausea, etc. • 15-30 hours after: convulsive activity • 1-2 days after: delirium tremens (disturbing hallucinations, delusions, agitation, confusion, hyperthermia & tachycardia) • Can last 3-4 days & potentially lethal

17. Alcohol • Chronic drinking extensively damages the brain • Indirectly causes Korsakoff’s syndrome (memory loss, sensory & motor dysfunction, dementia) • Increases likelihood of stroke • Reduces flow of Ca2+ into neurons by affecting ion channels • Interferes with 2nd messengers • Disrupts GABAergic & glutamatergic transmission • Triggers apoptosis • Also a teratogen • Can cause fetal alcohol syndrome: brain damage, mental retardation, poor coordination, etc.

20. Marijuana • From the cannabis plant • Most commonly smoked but can also be ingested orally • THC is the primary psychoactive chemical, but marijuana also contains 80+ other cannabinoids • “Social” doses tend to have subtle effects, but high doses impair psychological functioning • STM impaired, failure in multistep processes, slurred speech, difficulty having conversations, emotional intensification, sensory distortion, etc. • Low addiction potential (but possible) • Withdrawals rare • Some medical benefits: block seizures, reduce anxiety, pain & symptoms of MS, etc. • Works on receptors of endocannabinoids

21. Cocaine • Stimulants: drugs with the primary effect of increasing neural & behavioral activity • Cocaine is most commonly snorted or injected • Crack: smokable form of cocaine • Use as local anesthetic (although now replaced with synthetics such as lidocaine) • Psychological effects: feeling of well-being, self-confident, alert, energetic, friendly, outgoing, figety& talkative; decreased desire for food & sleep • During a binge period of high cocaine intake over a few days, a tolerance can develop • Cocaine psychosis: psychotic behavior accompanying a cocaine binge • Tolerance develops for most effects of cocaine, but there is sensitization to motor & convulsive effects

22. Other Stimulants • Even caffeine is classified as a stimulant drug • Amphetamine (speed): • Usually consumed orally • Similar effects to cocaine • Methamphetamine: • More potent, smokable, crystalline form • MDMA (ecstasy): • Another potent form; taken orally • Cocaine & these stimulants work by blocking dopamine transporters in the presynaptic membrane that normally remove dopamine from the synapse • Results in an increased amount of DA in the synapse; has agonistic effects

23. Long-term effects of stimulants • Habitual MDMA users have deficits in performance on neuropsychological tests, problems with dopamingergic & serotonergic neuron functioning, abnormalities in cortex & limbic system • Methamphetamine use results in decreased brain volume

24. Opiates • Opium’s primary psychoactive ingredients are morphine & codeine (opiates) • Function by binding to the receptors of the body’s natural opiates (endorphins & enkephalins) • Effective analgesics (painkillers), treat cough & diarrhea • Highly addictive yet surprisingly minor long term health problems

25. Opiates • Heroin: a semi-synthetic opiate • More easily crosses the BBB; more potent • Commonly injected (IV) • Creates a rush of intense pleasure followed by drowsy euphoria • Withdrawals within 6-12hrs; flu-like symptoms • Death from overdose common • Treatment with methadone, an opiate with similar effects, minus the desirable pleasure feelings • Alternate treatment with buprenorphine, which has a high & long-lasting affinity for opiate receptors, blocking other opiates from binding

26. Theories of Addiction • Physical-dependence theories of addiction • Drug user is stuck in a loop of drug taking & withdrawals due to physical dependence • Early treatment programs based on this theory; allowed addicts to withdraw in a hospital; however, once released, many relapsed • Detoxified addicts: addicts with no drugs in their system & are no longer experiencing withdrawal symptoms • Positive-incentive theories of addiction • Addicts take drugs to obtain the positive effects, not just to avoid withdrawals • Use driven by cravings • Most researchers now assume the primary factor in addiction is the pleasurable effects of the drug

27. Theories of Addiction • Addicts often report a huge discrepancy between the positive-incentive value (anticipated pleasure) & hedonic value (pleasure actually experienced) of a drug • Incentive-sensitization theory: • With repeated use, the positive-incentive value increases • Highly motivates individual to do the drug again • The pleasure of taking the drug isn’t the basis of addiction, instead it is the anticipated pleasure (wanting/craving the drug) • Over repeat usage, the actual pleasure decreases (with tolerance) but the anticipated pleasure increases (with sensitization) • Essentially an addict constantly chases a high they will never get

28. Relapse • Main problem in treating drug addicts is preventing those who stop taking the drug from relapsing (return to taking a drug after a period of voluntary abstinence) • Stress tends to be a major factor in relapse • Drug priming (single exposure to formerly abused drug) can lead to major relapse • Exposure to environmental cues associated with the former addiction can lead to relapse • Ex: people, places, objects

29. Pleasure Centers of the Brain • Rats, humans, etc. will administer electrical stimulation to specific areas of their brain (intracranial self-stimulation) • In some areas, rats will push the button endlessly until they become too exhausted to press it anymore • Led to research determining the pleasure centers of the brain • These brain areas are associated with pleasure from natural rewards (food, water, sex)

30. Pleasure Centers of the Brain • Mesotelencephalic dopamine system: • Important role in intracranial self-stimulation • System of DA neurons the project from midbrain to other cortical regions • DA neurons that originate in ventral tegmental area (VTA) with axons that project to the nucleus accumbens, within the mesocorticolimbic pathway, play a key role in the pleasure associated with natural rewards & addictive drugs • The reward pathway • Keep in mind that this reward system in the brain evolved to encourage adaptive behaviors, like eating & reproducing; addicts are simply using drugs to take advantage of this preexisting system

31. Brain Structures that Mediate Addiction • Initial Drug Taking: • In addition to the nucleus accumbens, 3 other brain areas are involved: • Prefrontal lobes (involved in decision to take a drug) • Hippocampus (provide info about previous relevant experiences) • Amygdala (coordinating emotional reactions to taking the drug) • Change to Craving & Compulsive Drug Taking • Changes in the how the striatum reacts to drugs seems to contribute to the development of addiction • Changes in dorsal striatum (area involved in habit formation) • Decrease of prefrontal cortex function in controlling drug-related behaviors • Relapse • PFC involved in priming-induced relapse • Amygdala involved in cue-induced relapse • Hypothalamus involved in stress-induced relapse