Ch 15 Drug Addiction & the Brain’s
Reward Circuits
Drug Administration & Absorption
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Psychoactive drugs:
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Drugs usually administered:
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Drugs that influence subjective experience & behavior by
acting on the nervous system
Oral ingestion
Injection
Inhalation
Absorption through mucus membranes
Method of administration affects the rate & degree of
impact
Drug Administration & Absorption
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Oral Ingestion:
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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:
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Common medical technique
Strong, fast & predictable
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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)
Drug Administration & Absorption
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Inhalation:
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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:
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Mucus membranes present in the nose (snorting), mouth &
rectum
Ex: cocaine
Drugs & CNS
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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
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Convert the drugs to nonactive form: drug metabolism
Drug Tolerance
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Drug tolerance: decreased sensitivity to a drug that develops over
repeat exposure
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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
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Ex: reduce # of receptors, decrease binding to receptor
Drug sensitization: increased sensitivity to a drug; opposite of
tolerance
Drug Withdrawal & Physical Dependence
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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
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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
Addiction
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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
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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
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Other addictions may be based on the same neural
mechanisms
Skip 15.2
5 Commonly Abused Drugs
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Tobacco
Alcohol
Marijuana
Cocaine (and other stimulants)
Opiates (heroin & morphine)
Tobacco
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The major psychoactive ingredient of tobacco is nicotine
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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
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Acts on cholinergic receptors in the brain
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
Tobacco
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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)
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And other cancers: larynx, mouth,
esophagus, kidneys, pancreas, bladder
& stomach
Increased likelihood of cardiovascular
disease
Tobacco
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Smokers are actually more tense; smoking only seems to
relax them
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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
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Those who quit before age 30 live almost as long as nonsmokers
Alcohol
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Alcohol molecules are small and both fat &
soluble so they can invade all parts of the body
Classified as a depressant
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water
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%)
Alcohol
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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)
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Can last 3-4 days & potentially lethal
Alcohol
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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
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Can cause fetal alcohol syndrome: brain damage, mental
retardation, poor coordination, etc.
Marijuana
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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
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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
Cocaine
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Stimulants: drugs with the primary effect of increasing neural &
behavioral activity
Cocaine is most commonly snorted or injected
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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
Other Stimulants
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Even caffeine is classified as a stimulant drug
Amphetamine (speed):
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Methamphetamine:
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More potent, smokable, crystalline form
MDMA (ecstasy):
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Usually consumed orally
Similar effects to cocaine
Another potent form; taken orally
Cocaine & these stimulants work by blocking dopamine
transporters in the presynaptic membrane that normally
remove dopamine from the synapse
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Results in an increased amount of DA in the synapse; has agonistic
effects
Long-term effects of stimulants
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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
Opiates
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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
Opiates
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Heroin: a semi-synthetic opiate
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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
Theories of Addiction
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Physical-dependence theories of addiction
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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
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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
Theories of Addiction
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Addicts often report a huge discrepancy between the
positive-incentive value (anticipated pleasure) &
hedonic value (pleasure actually experienced) of a drug
Incentive-sensitization theory:
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With repeated use, the positive-incentive value increases
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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)
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Essentially an addict constantly chases a high they will never get
Relapse
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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
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Ex: people, places, objects
Pleasure Centers of the Brain
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Rats, humans, etc. will administer electrical stimulation to
specific areas of their brain (intracranial selfstimulation)
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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)
Pleasure Centers of the Brain
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Mesotelencephalic dopamine system:
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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
Brain Structures that Mediate Addiction
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Initial Drug Taking:
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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
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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
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PFC involved in priming-induced relapse
Amygdala involved in cue-induced relapse
Hypothalamus involved in stress-induced relapse