P1: Diseases and Disorders | neurosciencenotes

DISEASES AND DISORDERS

Research is also essential for the development of therapies for more than 1,000 nervous system disorders that affect more than 1 billion people worldwide.

cHILDHOOD DISORDERS

Autism
Attention Deficit Hyperactivity Disorder
Down Syndrome

Autism

Autism spectrum disorders (ASD) :
impaired social skills
verbal and nonverbal communication difficulties
narrow, obsessive interests or repetitive behaviors

Common associated symptoms include intellectual disabilities, seizures, and gastrointestinal problems.

One of every 110 babies born in the United States, approximately 40,000 new cases each year, is diagnosed with ASD, an incidence far greater than in the 1970s.

This increase is due to:

changes in diagnostic criteria
detection of subtler forms of autism
enhanced parent and clinician referral based on greater awareness.

Mounting evidence, however, indicates that there is a true increase in the number of children with autism.

As a result, research efforts are now focusing on the interplay between genetic and environmental components that might contribute to the diagnosis.

Based mainly on twin studies, ASDs are thought to be highly genetic; already, more than 100 genes have been linked to increased risk for autism. That said, however, there is currently no single genetic or biochemical biomarker specifically for autism, because no single gene mutation or biological change will predict the disorder. Therefore, at this time, there is no way to determine if a newborn child is at risk for autism.

For this reason, ASD is typically diagnosed based on behavioral symptoms detected in children about three years of age.

However, very sensitive measures of social engagement and interaction can detect differences in children between one and two years old, a time when many affected children exhibit abnormal, accelerated growth of the brain. This abnormal growth may indicate that brain development has gone awry, thus making it a potential marker for early evaluation.

In addition, recent evidence indicates that some forms of autism may be due to dysregulation of the immune system, either in the mother or the child. One day, genetic or other biological tests may complement behavioral indicators to allow earlier diagnosis and intervention, as well as the means to possibly prevent or reduce ASD symptoms.

Brain alterations in autism are subtle; there is no obvious change such as in Down syndrome or Alzheimer’s disease.

There is speculation that abnormal development of certain regions of the brain involved in language, cognition, and social communication leads to abnormal connections with other parts of the brain. Although no cure exists and no drugs for the major symptoms of autism have been developed, many affected children respond very well to specialized behavioral therapies based on learning theory, with earlier interventions leading to better outcomes. Many of the therapeutic approaches to autism are guided by an increased understanding of how the brain normally reacts to learning, bonding, and social challenge as it develops.

One final note: It is now recognized that many of the brightest and most creative individuals in history may have had subtle forms of ASD. Therefore, researchers and others working in the field need to be aware that some “higher functioning” people with autism do not want to be “cured.” Instead, they would like to be accepted for who they are. (Kim Peek, Derek Paravicini, Daniel Tammet, Kim and Flo Rainman).

Summary:

Odd behaviors; sometimes includes
- intellectual disabilities
- seizures
- GI problems

Became more common among the years

changes in diagnostic criteria
detection of subtler forms of autism
enhanced parent and clinician referral based on greater awareness.
general increase
- caused studying interplay of genes and environment
- Highly genetic but don't known exactly which genes cause (il y a environ 100)
- diagnosis based on behavioral symptoms @ 3 YO

Could be caused by:

Genes
abnormal, accelerated brain growth @ age 1-2
- development has gone awry
dysregulation of the immune system
- mother or child

Goal:

genetic or biological tests + behavioral indicators = earlier diagnosis and intervention
means to possibly prevent or reduce ASD symptoms

Attention Deficit hyperactivity Disorder

first described more than 100 years ago.

Characterized by

excessively inattentive, hyperactive, or impulsive behaviors,
ADHD affects an estimated 5 to 8 percent of school-age children.
as many as 60 percent of these children will continue to experience ADHD symptoms as adults.
Children with ADHD are more likely to have problems in school, graduating from high school, maintaining a job, abusing drugs, or having healthy relationships.

Symptoms appear by middle childhood

last for six months or longer, and
impair normal functioning to a significant degree in the following settings:
for children — at school, among friends, and at home; for adults — at work and at home.

no objective diagnostic test for ADHD exists. Diagnosis requires a comprehensive evaluation, including a clinical interview, parent and teacher ratings for children, and self and other ratings for adults.

Learning disorder and psychological testing may also be used to clarify if other disorders are present along with the ADHD or if other conditions that look like ADHD may be responsible for the behaviors in question.

Thorough evaluation is required because problems with attention can be triggered by many other conditions; in particular, adults may have attention issues along with other disorders such as depression.

Clues

strong genetic influence, esp components of Dp and Npe transmission
- Twin and family studies show that ADHD has a strong genetic influence
finding correlations between ADHD and differences in brain function:
Altered activity is often observed in circuits connecting:
- the cortex, the striatum, and the cerebellum, particularly in the right hemisphere.
delay in cortical development in some children with ADHD, although most individuals with ADHD do not outgrow the disorder as they mature. Rather, their symptoms often change as they grow older, with less hyperactivity as adults.
Problems with attention tend to continue into adulthood.
imaging studies have shown reduced catecholamine transmission in at least some patients with this disorder
- PFC circuits require an optimal level of cat stimulation, reduced cat transmission could lead to weakened prefrontal cortical regulation of attention and behavior and symptoms of ADHD

There is no cure for ADHD at this time.

Treatments

parent education
school-based interventions
medications such as stimulants (e.g., methylphenidate)
and newer, nonstimulant drugs.
Adults benefit from the same medications as children
Also find some behavioral therapies helpful.
The medications all act by enhancing catecholamine transmission.
Treatment effectiveness is different for everyone and at diff times of treatment

Down Syndrome

most frequent occurring chromosomal condition
appears in 1/691 babies or about 6,000 babies annually in the US
typically occurs when an extra copy of chromosome 21 (or part of its long arm)
- present in the egg or less commonly in the sperm (@ conception)
not known why this error occurs
it has not been linked to any environmental or behavioral factors, either before or during pregnancy
but the risk is markedly increased with the age of the mother.

At age 25, the risk is about 1 in 1,250 births; at age 40, it is 1 in 100.

Because of higher fertility rates in younger women, 80 percent of children with Down syndrome are born to women under 35 years of age.

Prenatal screening tests, such as the triple and quadruple screen blood tests, can accurately detect Down syndrome in about 70 percent of fetuses.

Definitive prenatal diagnoses can be obtained with either chorionic villus sampling or amniocentesis.

Down syndrome is associated

50 physical and developmental characteristics.

mild to moderate intellectual disabilities
low muscle tone
an upward slant to the eyes
a flat facial profile
an enlarged tongue
increased risk of congenital heart defects
- respiratory problems
- digestive tract obstruction.
babies develop as much, but slower
- they learn to sit, walk, talk, and toilet train
- Early intervention programs can begin shortly after birth and can help foster an infant’s development
age 40 show neurological damage similar to alzh
cognitive decline by 60

Modern Improvements

medical advances and a greater understanding of the potential of those with this condition, people with Down syndrome have been able to have longer and fuller lives.
educated in neighborhood schools
participating in community activities
find rewarding employment and relationships.

Although there is no cure for Down syndrome or means of preventing it, scientists are moving closer to understanding the role that the genes on chromosome 21 play in a person’s development.

There are several mouse models of Down syndrome that are allowing scientists to focus on molecular factors important in the condition.

Once this mystery is understood, researchers hope to decode the biochemical processes that occur in Down syndrome and learn how to treat or cure this disorder.

DYSLEXIA

Unlike speaking, whose evolutionary origins are very old, reading and writing are relatively recent human inventions.

thousand years ago that communities in scattered parts of the world realised that the thousands of spoken words are made up of a smaller number of separate sounds (44 phonemes in English) and that these can be represented by an even smaller number of visual symbols.

Learning these symbols takes time and some children experience exceptional difficulties.

As many as 1 in 10 of us may have had this condition, now known by its neurological name, developmental dyslexia.
8 to 10 percent of children in the United States have some form of learning disability involving difficulties in the acquisition and use of listening, speaking, reading, writing, reasoning, or mathematical abilities.
These problems often occur in people with normal or even high intelligence.
- their brains find the particular requirements of reading difficult to master.
Dyslexia, a specific reading disability, is the most common and most carefully studied of the learning disabilities.
affects 80% of all those identified as learning disabled, or as many as 15-20% of Americans.

Dyslexia is characterized:

difficulty in speaking and reading in children and adults who otherwise possess the intelligence, motivation, and schooling considered necessary for accurate and fluent reading.
Studies indicate that although there can be improvement, dyslexia is a persistent, chronic condition.
There is now a strong consensus that the central difficulty in most forms of dyslexia reflects a deficit within the language system — more specifically, in a component of the language system called phonology.
- This deficit results in difficulty in both oral language and reading.
There may be mispronunciations of words
lack of fluency in speech
hesitations before responding
word retrieval difficulties.
As a result, a person with dyslexia often needs time to summon a verbal response when questioned.
As children approach adolescence, one manifestation of dyslexia may be a very slow reading rate.
May casue low hope or self esteem, depression

Main points

Children may learn to read words accurately, but their reading will not be fluent or automatic, reflecting the lingering effects of a phonologic deficit.
Because they can read words accurately (albeit very slowly) dyslexic adolescents and young adults may mistakenly be assumed to have “outgrown” their dyslexia.
The ability to read aloud accurately, rapidly, and with good expression, as well as facility with spelling, may be most useful clinically in distinguishing students who are average from those who are poor readers.

Interesting Points

some languages more consistent in the relationship between letters and sounds, such as Finnish and Italian, slow reading may be the only manifestation of dyslexia at any age.
A range of investigations indicates that there are differences in brain regions between dyslexic and nonimpaired readers involving three important left hemisphere neural systems, two posteriorly (parietotemporal, occipito-temporal) and one anteriorly around the left inferior frontal region (Broca’s area).
Converging evidence derived from functional brain imaging indicates that dyslexic readers demonstrate a functional inefficiency in an extensive neural system in the posterior portion of the brain.
Brain imaging revealed altered patterns of functional activation in regions sensitive to visual motion.

The brain images that result from these studies are referred to as the neural signature of dyslexia.

runs in families, NOT explained by one or just a few genes.

Genome-wide association studies (GWAS) in dyslexia have so far identified genetic variants that account for only a very small percentage of the risk — less than 1 percent — making it unlikely that a single gene or even a few genes will identify people with dyslexia.

Current evidence suggests that dyslexia is best conceptualized within a multifactorial model, with multiple genetic and environmental risk and protective factors leading to dyslexia.

Learning Methods:

words can be segmented into smaller units of sound
these sounds are linked with specific letter patterns.
practice in reading stories, both to allow them to apply their newly acquired decoding skills to reading words in context and to experience reading for meaning and enjoyment.

Understanding the process of reading better may lead us to a way of overcoming or treating the problem.

Learning to read depends on:

recognise alphabetic visual symbols in their right order (orthography)
hear the separate sounds in words in their right order.
involves extracting what is called the phonemic structure, so that the symbols can be translated into the correct sounds.

most dyslexics are slow and inaccurate at analysing both the orthographic and phonological features of words.

The ability to sequence letters and sounds accurately depends on both visual and auditory mechanisms.

For unfamiliar words,letter has to be identified and put in the right order.
not as easy as it sounds, eyes make small movements one letter to the next.
the letters are identified during each fixation of the eye but order is percieved where eye was pointing
What the eyes see has to be integrated with motor signals from the eye movement system; and it is with this visuomotor integration that many dyslexics have problems.
- specialised to respond to moving stimuli
- tf, important for tracking moving targets.

Visual control of the eye movement system is dominated by a network of large neurons known as the magnocellular system. It gets this name because the neurons (cells) are very large (magno).

This network can be traced right from the retina, through the pathway to the cerebral cortex and cerebellum, to the motor neurons of the eye-muscles.
generates motion signals, during reading, when the eyes move off letters they are meant to be fixating.
motion error signal is fed back to the eye-movement system to bring the eyes back on target.
The magnocellular system plays a crucial part in helping to point the eyes steadily at each letter in turn, and hence in determining their order.

visual magnocellular system is mildly impaired in many dyslexics.

Look at brain tissue or test sensitivity to visual motion of dyslexics;

(it's poorer than normal + their brain wave responses to moving stimuli are abnormal).

The control of the eye in dyslexics is less steady; hence they often complain that letters seem to move around and change places when they are trying to read.

These visual confusions are probably the result of the visual magnocellular system failing to stabilise their eyes as well as it does in good readers.

Putting sounds into the right order

Many dyslexics also have problems putting the sounds of words in the right order so that they tend to mispronounce words (such as pronouncing lollypop as pollylop) and they are very bad at tongue twisters.
When they come to reading, they are slower and more inaccurate at translating letters into the sounds they stand for.
Like their visual problems, this phonological deficiency is probably rooted in a mild deficiency of basic auditory skills.

We distinguish letter sounds, called phonemes, by detecting the subtle differences in the sound frequency and intensity changes that characterise them. Detecting these acoustic modulations is carried out by a system of large auditory neurons that track changes in sound frequency and intensity. There is growing evidence that these neurons fail to develop as well in dyslexics as in good readers and that the categorical boundaries between similar sounds, such as ‘b’ and ‘d’, are harder for them to hear.

Many dyslexics show evidence of impaired development of brain cells, extending beyond the visual and auditory problems they have with reading. These are problems in neurons that form networks throughout the brain that seem to be specialised for tracking temporal changes.

The cells all have the same surface molecules by which they recognise and form contacts with each other, but which may make them vulnerable to antibody attack.

The magnocellular system provides a particularly large input to the cerebellum.
Interestingly, some dyslexics are remarkably clumsy and their handwriting is often very poor.
Neuroimaging and metabolic studies of the cerebellum have indicated that its function can be impaired in dyslexics and this may be at the root of their difficulties with handwriting.

believe the cerebellum is involved in much more than the execution of movements such as writing and speaking, even including aspects of cognitive planning.

If correct, deficits in cerebellar function could add to problems with learning to read, write and spell.

Treatments

many
different hypotheses about underlying cause.
Some focus on the magnocellular hypothesis
other accounts distinguish different forms of the acquired condition
ex. surface and deep dyslexia, which may require different kinds of treatment.
All rely on early diagnosis.
problems in sound processing result in some dyslexics going down the wrong path for learning about sounds using the brain’s normal mechanisms of plasticity.
ex. play computer games in which they hear sounds that have been slowed down to the point where phonemic boundaries are much clearer.
What is scientifically interesting about the idea is that perfectly normal brain processes interact with an early genetic abnormality to produce an exaggerated effect.

dyslexics may be slightly better than even good readers at some perceptual judgements such as colour distinctions and global, rather than local, shape discriminations. This hints at a possible explanation of why many dyslexics may be superior in seeing long-range associations, unexpected associations and at ‘holistic’ thinking in general. Remember that Leonardo da Vinci, Hans Christian Andersen, Edison and Einstein and many other creative artists and inventors were dyslexic.

Summary

chronic condition
most carefully studied
1/10 developmental dyslexia
8-10 % children have a linguistic LD
Phonologic deficit; difficulty in both oral language and reading

slowness at all ages is an indicator
fluency
hesitations
word retrieval
mispronunciations

Dyslexic and nonimpaired readers involving three important left hemisphere neural systems:

two posteriorly
- Parietotemporal
- Occipito-temporal
one anteriorly around the left inferior frontal region
- Broca’s area

Reading Requires

Seeing order (orthography)
hearing order
speaking it in order (phonemic structure)

ADDICTION

Drug abuse is one of the nation’s most serious health problems.

About 9 percent of Americans, more than 22 million people, abuse drugs on a regular basis.

Drug abuse, including alcohol and nicotine, is estimated to cost the United States more than $600 billion each year.

If continued long enough, drug abuse can eventually alter the very structure and chemical makeup of the brain, producing a true brain disorder.

This disorder is called drug addiction or drug dependence.

Drug addiction is characterized by:

a pathological desire for drugs,
such that drug-seeking and drug-taking behaviors occupy an inordinate amount of
an individual’s time and thoughts,
at the expense of other activities.
persist despite many adverse consequences.
difficulty controlling frequency of use and terminating use, despite a stated desire to do so.
initially experiment with drugs for many different reasons,
most drugs of abuse (pleasure or remove stress and emotional pain).

Neuroscientists have found that almost all abused drugs produce pleasure by activating a specific network of neurons called the brain reward system.

The circuit is normally involved in an important type of learning that helps us stay alive.

It evolved to mediate the pleasurable and motivating effects of natural rewards

eating when we are hungry

drinking when we are thirsty.

behavior=feelings of pleasure = MUST repeat

Drugs can activate this same system, thus promoting continued drug use.

Abused drugs alter the ways NTs carry messages from n to n

Some drugs mimic neurotransmitters, while others block them.
others alter the way NTs are released or inactivated.

brain reward system is activated inappropriately: drugs alter the chemical messages sent among neurons in this circuit.

addiction requires more than the activation of the brain reward system.
drugs themselves change the brain of susceptible individuals in complex ways
- leading to symptoms of addiction.
In addition to the brain reward system, brain regions that are changed by drugs include those involved in executive functions and judgment.
- important in inhibiting behavior and in decision-making.

addiction is influenced by many factors

Motivation for drug use

ex. opioids to get high may get addicted, but people who use them properly to relieve pain rarely do.

Genetic susceptibility and environmental factors, can alter the way that people respond to drugs

ex. stress

The characteristics of the drugs themselves, such as how quickly they enter the brain, also play a role in addiction.

development of tolerance — the progressive need for a higher drug dose to achieve the same effect — varies in different people,

drug dependence — the adaptive physiological state that results in withdrawal symptoms when drug use stops.

Tolerance and dependence are standard responses of the brain and body to drugs. At the same time, the individual is starting to feel that it is impossible to live without a drug. When this feeling starts to grow, it means that the person is developing a motivational form of dependence as well.

An important question for addiction research is to understand how these many factors interact to predispose individuals to addiction. The hope is that the knowledge and insight into abuse and addiction that emerge from this research will lead to new therapies.

Drugs differ in their dependence liability

high risk: cocaine, heroin and nicotine

lower risk: alcohol, cannabis, ecstasy and amphetamines

Drugs by Dependancy Rates:

Nicotine
Heroin
Cocaine
Alcohol
Marijuana
Tranquilizers and prescription meds

Drugs by Popularity:

Alcohol
Nicotine
Marijuana
Cocaine
Heroin
Tranquilizers and prescription meds

primary sites of action are all different, these drugs share an ability to promote release of dopamine in certain brain regions.

not necessarily akin to triggering a “pleasure” mechanism, it is thought that the drug-induced release of dopamine may be an important final common pathway of “pleasure” in the brain. It represents the signal that prompts a person to carry on taking the drug.

Nicotine

In 2009, more than 70 million Americans smoked.
>100,000 people die every year in Britain from smoking related diseases
kills more than 440,000 U.S. citizens each year
- proof that smoking can be fatal, nicotine still is one of the most widely abused substances.
- (more than alcohol, cocaine, heroin, homicide, suicide, car accidents, and HIV combined)
leading preventable cause of death in the US
overall cost of smoking in the US is estimated to be $193 billion each year.
acetylcholine; activate natural alerting mechanisms in the brain
concentrate and soothing effect
highly addictive and many smoke to avoid the unpleasant signs of withdrawal
no effect on the brain, tobacco smoke damaging to lungs and lt exposure can lead to lung cancer and also to other lung and heart diseases

This drug can act as both a stimulant and a sedative.

Nicotine, the addicting substance in tobacco, acts through the well-known acetylcholine nicotinic receptor.

Nicotine stimulates the adrenal glands, and the resulting discharge of epinephrine causes a “kick” — a sudden release of glucose paired with an increase in blood pressure, respiration, and heart rate.

releases dopamine in the brain regions that control motivation, which is one reason that people continue to smoke.

Treatment

understanding of addiction, coupled with identification of nicotine as an addictive drug, has been instrumental in the development of treatments.
Nicotine gum, the transdermal patch, nasal spray, and inhalers are equally effective in treating the more than one million people addicted to nicotine.
These techniques are used to relieve withdrawal symptoms and are helpful in that they produce less severe physiological alterations than using tobacco products.
- transdermal patch
- Nicotine gum
- nasal spray
- inhalers
- provide users with lower overall nicotine levels than they receive with tobacco and totally eliminate exposure to smoke and its deadly contents.
The first non-nicotine prescription drug, bupropion, an antidepressant, has been approved for use as a pharmacological treatment for nicotine addiction.
An exciting advance is the use of varenicline for smoking cessation.
- This medication interacts directly with the acetylcholine nicotinic receptor in a key part of the brain’s reward circuitry and prevents nicotine from activating this circuit.
Behavioral treatments also are important in helping an individual learn coping skills for both shortand long-term prevention of relapse.

Psychostimulants

cocaine and amphetamines.

In 2009, in the US, an estimated 4.8 million people age 12 and older had abused cocaine.

Cocaine

plant-derived chemical can cause pleasurable sensations & powerful psychostimulant
Like the amphetamines, cocaine makes more dopamine and serotonin available in the brain
dangerous, users esp. of "crack", can become violent and agro, and life threatening risk of overdose
cost can cause crime
users often go on binges, consuming a large amount of the drug in just a few days.
crash occurs after this period of intense drug-taking, resulting in such symptoms as emotional and physical exhaustion and depression.

Symptoms may come from

actual shutdown, or crash, in dopamine and serotonin function
an increased response of the brain systems that react to stress

Vaccines to produce antibodies to cocaine in the bloodstream are in clinical trials.

A popular, chemically altered form of cocaine, crack, is smoked.

enters the brain in seconds, producing a rush of euphoria and feelings of power and self-confidence.
Alterations in dopamine activity in the accumbens, induced by chronic cocaine intake, are thought to result in a progressively increasing motivation to take the drugs, eventually leading to addiction.

Amphetamines

man-made chemicals that include “Dexedrine”, “Speed” AND methamphetamine derivative called “Ecstasy”
release two naturally occurring NTs:
dopamine - explains the strong arousal and pleasurable effects of amphetamines.
serotonin - account for ability to cause a sense of well-being and dream-like state (include hallucinations)

Dexedrine and Speed promote mainly dopamine release, Ecstasy more serotonin
more powerful hallucinogen d-LSD also acts on serotonin mechanisms in the brain
Amphetamines are powerful psychostimulants and they can be dangerous - especially in overdose. Animal experiments have shown that Ecstasy can cause a prolonged, perhaps permanent reduction of serotonin cells
Frightening schizophrenia like psychosis can happen after Dexedrine and Speed
A form of methamphetamine that can be smoked, “crystal meth,” also has become popular.
research uncovering the serious damage can occur in several parts of the brain from some of da drugs

MDMA, called “adam,” “ecstasy,” or “XTC” on the street, is a synthetic psychoactive drug with hallucinogenic and amphetamine-like properties.
Users encounter problems similar to those found with the use of amphetamines and cocaine.
Recent research also links chronic ecstasy use to long-term changes in those parts of the brain critical for thought, memory, and pleasure.
Ecstasy serotonin
more powerful hallucinogen d-LSD also acts on serotonin mechanisms in the brain

The key biochemical factor underlying the reinforcing effects of psychostimulant drugs is their ability to greatly elevate the brain chemical dopamine in specific brain regions, such as the nucleus accumbens.

Alcohol

Although legal, alcohol is addictive.

Nearly 17.6 million people abuse alcohol or are alcoholic
Fetal alcohol syndrome, affecting about 1 to 3 of every 1,000 babies born in the United States, is the leading preventable cause of mental retardation.
>30,000 people die every year in Britain from alcohol-related diseases
~1/10 regular drinkers will become dependent alcoholics
dampen excitatory messages and promote inhibition
Lt damages the body, especially the liver, and can cause permanent damage to the brain
Pregnant + alc = damaged brains and low IQ’s

alcohol abuse (alcoholism) and alcohol addiction (alcohol dependence) are among the nation’s major health problems.

genetic and environmental factors contribute to alcoholism, no single factor or combination of factors enables doctors to predict who will develop an addiction to alcohol. (so far)

Cirrhosis

scarring of the liver
main chronic health problem associated with alcohol addiction.
Other chronic liver diseases are responsible for more than 29,000 deaths each year.
The annual cost of alcohol abuse and addiction is estimated at $185 billion.

Ethanol

active ingredient in alcoholic beverages

reduces anxiety, tension, and behavioral inhibitions.
In low doses
- act as a stimulant
higher doses
- acts as a depressant

In both cases, it significantly alters mood and behavior.

Too much alcohol can also cause heat loss and dehydration.

Ethanol and the Brain

easily absorbed into the bloodstream and the brain
affects several neurotransmitter systems

interaction with the GABAr can

calm anxiety
impair muscle control
delay reaction time.

At higher doses, alcohol decreases the function of NMDAr (Gm).

can cloud thinking and eventually lead to coma.

In addition, animal research has shown that alcohol works by activating the endogenous opioid system.

This means that susceptible individuals may feel an opioid-like euphoria from their own endorphins when they drink.

Earlier, a medication called naltrexone had been developed for heroin addiction, which also affects the opioid system.
works by blocking opioid receptors.
Researchers thought that this medication might be effective for alcoholics as well. Clinical trials began in 1983, and in 1995, the U.S. FDA approved naltrexone for the treatment of alcoholism.

A central group of structures is common to the actions of all drugs.

include a collection of dopamine-containing neurons found in the VTA.

These neurons are connected to the nucleus accumbens and other areas, such as the prefrontal cortex.

Cocaine is one drug that exerts its effects mainly through this system.

Opiates also act in this system and many other brain regions, including the amygdala.

Alcohol activates the core reward system and additional structures throughout the brain because it acts where GABA and glutamate are used as neurotransmitters.

Marijuana

distorts
- perception
- sense of
  - time
  - space
  - self.
can produce intense anxiety
has been used at least once by nearly 1/2 the population of Britain <30
~1/10 become dependent, which people who sell the drug are well aware of
endocannabinoids
control of muscles
regulating pain sensitivity
pleasurable and relaxing, dream-like state; perception of sounds, colours and time is subtly altered
no one died from an overdose, may experience unpleasant panic attacks after large doses
smoke contains much the same mixture of poisons as cigerettes
smokers tend to develop lung diseases and they run the risk of developing lung cancer
incompatible with the skill of driving and with intellectually demanding work; experiments have established that people intoxicated with cannabis are unable to carry out complex mental tasks.
some evidence that heavy use by young people might trigger the mental illness schizophrenia in susceptible individuals.

radioactive tracing studies, tetrahydrocannabinol (THC) binds to specific receptors

cannabinoid receptors
- many coordinate movement.

This may explain why people who drive after they smoke marijuana are impaired.

Hippocampus

involved with memory storage and learning
contains many receptors for THC
insight into why heavy users or those intoxicated on marijuana
poor short-term memory
problems processing complex information.

Cannabinoid receptors

bind to natural internal chemicals termed endocannabinoids, one of which is called anandamide.
develop medications that target the endogenous, or internal, cannabinoid system.
goal: beneficial in treating brain disorders, ex. addiction, anxiety, and depression.

Opiates

Humans have used opiate drugs, such as morphine, for thousands of years.

Monkeys and rats readily self- administer heroin or morphine and, like humans, will become tolerant and physically dependent with unlimited access.

Withdrawal symptoms range from

mild, flulike discomfort to
severe muscle pain
stomach cramps
diarrhea
unpleasant mood.

Opiates and the Brain

increase the amount of dopamine released in the brain reward system and mimic the effects of endogenous opioids.
Heroin injected into a vein reaches the brain in 15 to 20 seconds and binds to opiate receptors found in many brain regions, including the reward system.
Activation of the receptors in the reward circuits causes a brief rush of intense euphoria, followed by a couple of hours of a relaxed, contented state.
create effects like those elicited by the naturally occurring opioid peptides.
- relieve pain
- depress breathing
- cause nausea and vomiting
- stop diarrhea
all important medical uses.

man-made chemical derivative of the plant product morphine
NTs known as endorphins (pain control) drugs copy their actions are valuable in med.
injected/smoked (immediate) possibly due to an effect of endorphins on reward mechanisms
highly addictive, as dependence develops, these pleasurable sensations quickly subside to be replaced by an incessant “craving”
It is a very dangerous drug that can kill in even modest overdose (it suppresses breathing reflexes)

large doses

heroin->breathing shallow or stop it altogether ->cause of death in thousands of people who have died of heroin OD

treatment

standard for opiate addiction involves methadone

a long-acting oral opioid that helps keep
craving
withdrawal
and relapse under control
helps opiate addicts rehabilitate themselves by preventing withdrawal symptoms that can motivate continued drug use.

Naloxone and naltrexone are available medications that act as antagonists at opioid receptors; that is, they can curb the allure of opiates by blocking the opiate receptors so that opiates produce no pleasurable effects when they are taken.

The blockers alone are sometimes useful for addicts who are highly motivated to quit.

scientists are developing a long-lasting version of naltrexone that needs to be taken only once a month.

Another medication used to treat heroin addiction, buprenorphine, causes a weaker effect on the receptors than methadone and creates only a limited high, which deters an addict from abusing the medication itself.

Buprenorphine has been prescribed for more than 500,000 patients in the US

Club Drugs

Ecstasy
herbal ecstasy
rohypnol (“roofies”)
GHB (gamma hydroxy-butyrate)
ketamine

are among the drugs used by some teens and young adults as part of raves and trances.

These drugs

increase stamina

produce intoxicating highs

said to deepen the rave or trance experience.

Recent research, however, is uncovering the serious damage that can occur in several parts of the brain from use of some of these drugs.

MDMA, called “adam,” “ecstasy,” or “XTC” on the street, is a synthetic psychoactive drug with hallucinogenic and amphetamine-like properties.

Users encounter problems similar to those found with the use of amphetamines and cocaine.

Recent research also links chronic ecstasy use to long-term changes in those parts of the brain critical for thought, memory, and pleasure.

Rohypnol, GHB, and ketamine

CNS depressants

colorless, tasteless, and odorless

easily to beverages and unknowingly ingested

date-rape drugs

alcohol+rohypnol= incapacitate victims and prevent them from resisting sexual assault.
- Rohypnol may be lethal when mixed with alcohol and other depressants.
GHB has been abused for its euphoric, sedative, and anabolic effects.
- Since about 1990 in the United States
- associated with sexual assault.
Ketamine =“Special K”
- fast-acting general anesthetic
- sedative, hypnotic, analgesic, and hallucinogenic properties
- marketed in the US and foreign countries as a general anesthetic

alcohol+rohypnol= incapacitate victims and prevent them from resisting sexual assault.

Rohypnol may be lethal when mixed with alcohol and other depressants.

Since about 1990 in the United States, GHB has been abused for its euphoric, sedative, and anabolic (body-building) effects.

associated with sexual assault.

Ketamine

“Special K,”

CNS depressant abused as a date-rape drug.

fast-acting general anesthetic.

sedative, hypnotic, analgesic, and hallucinogenic properties.

It is marketed in the United States and a number of foreign countries as a general anesthetic

Many users tend to experiment with a variety of club drugs in combination.

This practice creates a larger problem, because combinations of any of these drugs, particularly with alcohol, can lead to unexpected adverse reactions and even death after high doses.

Physical exhaustion also can enhance some toxicities and problems.

general anesthetic — a drug that brings about a reversible loss of consciousness

The Neuroscience Center

DISEASES AND DISORDERS

cHILDHOOD DISORDERS

DYSLEXIA

ADDICTION

DRUGS AND THE BRAIN

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