Drug Addiction & Risky Business

1. Drug Addiction & Risky Business June 30, 2011

2. Prospect Gambling Experiment http://myweb.fsu.edu/djcooper/teaching/prospect.pdf

3. Prospect Gambling • For each pair, you will be asked to choose one of the two gambles. You should record your choice on a sheet of paper by writing either Gamble A or Gamble B for each pair. • Some of the gambles will have negative payoffs. The maximum amount you can lose is $4.

4. Impulse &Risk-Seeking Behaviors

5. Impulsivity Predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences Best understood through examining disorders associated with impulsivity Impulse-Control Disorders Seeking a small, short-term gain at the expensive of a large, long-term loss IED, pathological gambling, trichotillomania, kleptomania Seems to be associated with serotonin

6. Serotonin Low levels of serotonin metabolites correlate with risk-taking Vervet monkeys given 5-HT agonist: become dominant 5-HT 1B KO mice are quicker to attack opponent 5-HT controls risk taking, which impacts aggressive behavior

7. Risk-Taking & The Brain • People who seek risks can be thought of as “reducers”: Their brains reduce the level of incoming stimuli, thus decreasing their excitement • Monoamine Oxidase (MAO) plays a role in this: Low levels of MAO are associated with high risk-taking • MAO regulates levels of: • Norepinephrine (arousal) • Dopamine (pleasure & reward) • Serotonin (inhibits arousal) • High risk-takers may have decreased levels of norepinephrine and dopamine

8. I like to keep moving I make friends easily I like lots of physical activity I feel a lot of tension I talk more than the average person I enjoy lots of environmental stimulation (excitement, activity) My home life is not always happy When things get quiet, I like to stir things up I am usually restless I don’t think I’m as happy as other people I get angry often I like being the center of attention at social gatherings I feel very anxious if I cannot find a release for my anger It’s hard for me to stick with various projects at work and home I will fight with someone, even if I know I am wrong I’m not known as a hard and steady worker I feel relief after I release my anger through some avenue Sometimes I act impulsively I find it difficult to relax and unwind I live with many regrets from past actions Impulsivity Assessment http://www.roberts.edu/LifeAtRoberts/ResidentLife/counselingCenter/Documents/Impulsivity%20Assessment.pdf Used with permission of Paul Hirshfield, Hirshfield and Associates, 529 Pharr Road, Atlanta, Georgia 30305

9. Neurobiology of Reward

10. The Reward Pathway

11. striatum striatum striatum hippocampus hippocampus hippocampus frontal cortex frontal cortex frontal cortex substantia nigra/VTA substantia nigra/VTA substantia nigra/VTA nucleus accumbens nucleus accumbens nucleus accumbens raphe raphe raphe Dopamine Pathways • Functions • reward (motivation) • pleasure,euphoria • motor function • (fine tuning) • compulsion • perserveration • decision making Serotonin Pathways • Functions • mood • memory • processing • sleep • cognition From Lecture by Glen R. Hanson, NIDA

12. Dopamine-containing neurons are the pleasure generating cells of the brain From Lecture by Glen R. Hanson, NIDA

13. stimulation vesicle Neuronal terminal • Drug : • cocaine • ritalin transporter Vmat /serotonin • How some drugs of abuse cause dopamine release: • opioids narcotics (activate opioid receptors) • nicotine (activate nicotine receptors) • marijuana (activate cannabinoid receptors) • caffeine • alcohol (activate GABA receptors; an inhibitory transmitter) DA/5HT From Lecture by Glen R. Hanson, NIDA

14. transporter Vmat serotonin/ • Release DA from vesicles and reverse • transporter DA/5HT • Drug Types: • Amphetamines • -methamphetamine • -MDMA (Ecstasy) From Lecture by Glen R. Hanson, NIDA

15. Effects of Drugs on Dopamine Release COCAINE AMPHETAMINE Accumbens 1100 Accumbens 400 1000 900 DA 800 DA 300 DOPAC 700 DOPAC % of Basal Release HVA HVA 600 % of Basal Release 500 200 400 300 100 200 100 0 0 0 1 2 3 4 5 hr Time After Amphetamine Time After Cocaine 250 NICOTINE ETHANOL 250 Accumbens Dose (g/kg ip) 200 Accumbens 200 Caudate 0.25 0.5 150 % of Basal Release 1 2.5 % of Basal Release 150 100 0 1 2 3 hr 0 1 2 3 4 5 hr 100 0 0 0 1 2 3 4hr Time After Nicotine Time After Ethanol Much greater Activity than any Other drug of abuse -causes neurotoxicity Source: Di Chiara and Imperato From Lecture by Glen R. Hanson, NIDA

16. The Addicted Brain From Lecture by Leonard Howell, Emory University

17. CRITERIA FOR SUBSTANCE ABUSE • A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period: • 1. recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absence, suspensions, or expulsions from school; neglect of children or household); • 2. recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use); • 3. recurrent substance-related legal problems (e.g., arrests for substance- related disorderly conduct); • 4. continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights). • B. The symptoms have never met the criteria for Substance Dependence for this class of substance. From Lecture by Leonard Howell, Emory University

18. From Lecture by Leonard Howell, Emory University

19. control cocaine abuser Decreases in Metabolism in OrbitoFrontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 From Lecture by Glen R. Hanson, NIDA

20. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. From Lecture by Glen R. Hanson, NIDA

21. Dopamine Transporter Loss AfterHeavy Methamphetamine Use Comparison Subject METH Abuser Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. From Lecture by Glen R. Hanson, NIDA

22. Following Drug Addiction • Ability to experience rewards is impaired. • Commonalities in underlying neurobiological forces can often lead to co-morbid conditions. • Genetic • Structural/Anatomical • Neurochemical • Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness. From Lecture by Glen R. Hanson, NIDA

23. Commonalities From Lecture by Glen R. Hanson, NIDA

24. System Hijack! Drugs of Abuse http://learn.genetics.utah.edu/content/addiction/drugs/mouse.html

25. Common Drugs of Abuse

26. Commercials

27. Rodent Self-Administration http://science-education.nih.gov/supplements/nih2/Addiction/guide/pdfs/nih_drug.pdf

28. What Drug is Being Self-Administered? When?

29. Current Research David Weinshenker, PhD Emory University

30. Writing Formal Lab Reports