Ch 15 Drug Addiction & the Brain’s Reward Circuits

Drug Administration & Absorption

Psychoactive drugs: Drugs that influence subjective experience &

behavior by acting on the nervous system Drugs usually administered:

1. Oral ingestion2. Injection3. Inhalation4. Absorption through mucus membranes

Method of administration affects the rate & degree of impact

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)

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

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

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 tolerance1. Metabolic: reduces the amount of drug getting to the sites

of action2. 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

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

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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5 Commonly Abused Drugs1. Tobacco2. Alcohol3. Marijuana4. Cocaine (and other stimulants)5. Opiates (heroin & morphine)

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

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

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

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%)

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 activity3. 1-2 days after: delirium tremens (disturbing hallucinations,

delusions, agitation, confusion, hyperthermia & tachycardia)

Can last 3-4 days & potentially lethal

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.

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

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

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

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

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

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

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

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

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

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)

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

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