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: 1. Oral ingestion 2. Injection 3. Inhalation 4. 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 1. Metabolic: reduces the amount of drug getting to the sites of action 2. 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 1. Tobacco 2. Alcohol 3. Marijuana 4. Cocaine (and other stimulants) 5. 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 1. 5-6 hours after: severe tremors, agitation, headache, nausea, etc. 2. 15-30 hours after: convulsive activity 3. 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 2 nd 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: 1. Prefrontal lobes (involved in decision to take a drug) 2. Hippocampus (provide info about previous relevant experiences) 3. 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