1. Case Study#2: Effect of Alcohol/Drugs on Teen Brain Yehuda Ben-Shahar, PhD Department of Biology, Washington University in St. Louis

2. Drosophila melanogaster

3. Courtship as a model for social behaviors

5. Drug use in teenagers – what does it do to their brains? Short-term versus long-term effects of use of, and addiction to drugs

6.  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!

7. Why should we care? Data from the NIDA InfoFacts: High School and Youth Trends

8. Drugs – mode of action Most known drugs affect neurotransmission in the brain – typically by acting on specific receptors

9. 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

10. 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.

11. 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

12. 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

13.  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

14. 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

15. Marijuana

16. 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

17. 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