Case Study#2: Effect of

Alcohol/Drugs on Teen Brain Yehuda Ben-Shahar, PhDDepartment of Biology, Washington University in St. Louis

Drosophila melanogaster

Courtship as a model for social behaviors

Drug use in teenagers –

what does it do to their

brains?

Short-term versus long-term effects of use of, and addiction to drugs

Huntington’s disease = 100%

Sickle Cell Anemia = 100%

Obesity = 60%-90%

Breast Cancer = 30%

Asthma = 25%

Type II Diabetes = 26%

Alcohol dependence = 38%-64%

Nicotine dependence = 75%

Heritability

But… the environment is a key factor as well!

Why should we care?

Data from the NIDA InfoFacts: High School and Youth Trends

Drugs – mode of action

Most known drugs affect neurotransmission in the brain – typically by acting on specific receptors

Alcohol, Barbiturates, and Benzodiazepines

These drugs exert their effects mostly via the gamma-Aminobutyric acid (GABA) signaling pathway

GABA is the principle inhibitory neurotransmitter in the mammalian brain

Alcohol, Barbiturates, and Benzodiazepines

Short-term effects Potentiates GABA-activated

Cl- channels Allows more Cl- to cross the

membrane Increases inhibition in the

post-synaptic cell Increases turnover of

norepinephrine and dopamine,

Decreases transmission in acetylcholine systems

Increases production of beta-endorphin in the hypothalamus.

Alcohol, Barbiturates, and Benzodiazepines

Long-term effects Damage to the frontal lobes

of the brain An overall reduction in brain

size Increase in the size of the

ventricles Alcoholism can cause

Vitamin B-1 (thiamine) deficiency, leading to Wernicke-Korsakoff syndrome, characterized by amnesia, apathy and disorientation.

Embryonic rat brain

Use of alcohol despite severe social or physical consequences.

Characterized by (some or all of the following):

Tolerance

Withdrawal

Uncontrollable use

Social, occupational, recreational consequences

Use continued despite knowledge of alcohol-related harm

Alcohol Dependence

First behavioral disorder to have a validated genetic finding

Subjects of Asian descent noted to have facial flushing and decreased tolerance compared to subjects of European descent

1980 – Found 50% of Japanese post-mortem liver extracts were missing aldehyde dehydrogenase (ALDH) isozyme I

Genetics of Alcohol Dependence

Elevated ethanal (acetaldehyde) levels cause Facial flushing Nausea Tachycardia

Causes behavioral aversion to alcohol

1/3 susceptibility to alcoholism as compared to wild-type

Mechanism of disulfiram (Antabuse)

ALDH isozyme I deficiency

Marijuana

Marijuana

Short-term effects Delta-9 tetrahydrocannabinol or

"THC” binds to cannabinoid receptors, which exist in many areas of the brain

Affects the levels of norepinephrine, dopamine, serotonin, and GABA in the brain

Relaxation

Reduced coordination

Reduced blood pressure

Sleepiness

Disruption in attention

An altered sense of time and space

Marijuana

Long-term effects Whether marijuana usage leads to addiction or long-

term mental abnormalities is still controversial and a topic of current research

Data suggest that onset of schizophrenia in susceptible individuals is associated with cannabis use

Because marijuana contains many other chemicals that are also inhaled, it leads similar respiratory problems as smoking cigarettes, as well as cancer and immune deficiencies