Drug Addiction & Risky Business

Drug Addiction & Drug Addiction & Risky BusinessRisky Business

June 30, 2011June 30, 2011

Prospect Gambling Prospect Gambling ExperimentExperiment

http://myweb.fsu.edu/djcooper/teaching/prospect.pdf

http://myweb.fsu.edu/djcooper/teaching/prospect.pdf

Prospect GamblingProspect Gambling

For each pair, you will be asked to choose For each pair, you will be asked to choose one of the two gambles. You should record one of the two gambles. You should record your choice on a sheet of paper by writing your choice on a sheet of paper by writing either Gamble A or Gamble B for each pair. either Gamble A or Gamble B for each pair.

Some of the gambles will have negative Some of the gambles will have negative payoffs. The maximum amount you can lose payoffs. The maximum amount you can lose is $4. is $4.

Impulse &Impulse &Risk-Seeking Risk-Seeking

BehaviorsBehaviors

ImpulsivityImpulsivity Predisposition toward rapid, unplanned Predisposition toward rapid, unplanned

reactions to stimuli without regard to reactions to stimuli without regard to negative consequencesnegative consequences

Best understood through examining Best understood through examining disorders associated with impulsivitydisorders associated with impulsivity

Impulse-Control DisordersImpulse-Control Disorders– Seeking a small, short-term gain at the Seeking a small, short-term gain at the

expensive of a large, long-term lossexpensive of a large, long-term loss– IED, pathological gambling, trichotillomania, IED, pathological gambling, trichotillomania,

kleptomaniakleptomania Seems to be associated with serotoninSeems to be associated with serotonin

SerotoninSerotonin Low levels of serotonin metabolites Low levels of serotonin metabolites

correlate with risk-takingcorrelate with risk-taking Vervet monkeys given 5-HT agonist: Vervet monkeys given 5-HT agonist:

become dominantbecome dominant 5-HT 1B KO mice are quicker to 5-HT 1B KO mice are quicker to

attack opponentattack opponent 5-HT controls risk taking, which 5-HT controls risk taking, which

impacts aggressive behaviorimpacts aggressive behavior

Risk-Taking & The BrainRisk-Taking & The Brain

People who seek risks can be thought of as People who seek risks can be thought of as “reducers”: Their brains reduce the level “reducers”: Their brains reduce the level of incoming stimuli, thus decreasing their of incoming stimuli, thus decreasing their excitementexcitement

Monoamine Oxidase (MAO) plays a role in Monoamine Oxidase (MAO) plays a role in this: Low levels of MAO are associated this: Low levels of MAO are associated with high risk-takingwith high risk-taking

MAO regulates levels of:MAO regulates levels of:– Norepinephrine (arousal)Norepinephrine (arousal)– Dopamine (pleasure & reward)Dopamine (pleasure & reward)– Serotonin (inhibits arousal)Serotonin (inhibits arousal)

High risk-takers may have decreased High risk-takers may have decreased levels of norepinephrine and dopaminelevels of norepinephrine and dopamine

Impulsivity AssessmentImpulsivity Assessment

1.1. I like to keep moving I like to keep moving 2.2. I make friends easily I make friends easily 3.3. I like lots of physical activityI like lots of physical activity4.4. I feel a lot of tensionI feel a lot of tension5.5. I talk more than the I talk more than the

average personaverage person6.6. I enjoy lots of I enjoy lots of

environmental stimulation environmental stimulation (excitement, activity)(excitement, activity)

7.7. My home life is not always My home life is not always happyhappy

8.8. When things get quiet, I like When things get quiet, I like to stir things up to stir things up

9.9. I am usually restless I am usually restless 10.10. I don’t think I’m as happy I don’t think I’m as happy

as other peopleas other people

11.11. I get angry oftenI get angry often12.12. I like being the center of I like being the center of

attention at social gatheringsattention at social gatherings13.13. I feel very anxious if I cannot I feel very anxious if I cannot

find a release for my anger find a release for my anger 14.14. It’s hard for me to stick with It’s hard for me to stick with

various projects at work and various projects at work and homehome

15.15. I will fight with someone, even I will fight with someone, even if I know I am wrongif I know I am wrong

16.16. I’m not known as a hard and I’m not known as a hard and steady workersteady worker

17.17. I feel relief after I release my I feel relief after I release my anger through some avenueanger through some avenue

18.18. Sometimes I act impulsivelySometimes I act impulsively19.19. I find it difficult to relax and I find it difficult to relax and

unwind unwind 20.20. I live with many regrets from I live with many regrets from

past actionspast actions

Used with permission of Paul Hirshfield, Hirshfield and Associates, 529 Pharr Road, Atlanta, Georgia 30305http://www.roberts.edu/LifeAtRoberts/ResidentLife/counselingCenter/Documents/Impulsivity%20Assessment.pdf

Neurobiology of Neurobiology of RewardReward

The Reward Pathway

Dopamine Pathways

Functions•reward (motivation)•pleasure,euphoria•motor function (fine tuning)•compulsion•perserveration•decision making

Serotonin PathwaysFunctions•mood•memory processing•sleep•cognition

nucleusaccumbens

hippocampus

striatum

frontalcortex

substantianigra/VTA

raphe

From Lecture by Glen R. Hanson, NIDA

nucleusaccumbens

hippocampus

striatum

frontalcortex

substantianigra/VTA

raphe

nucleusaccumbens

hippocampus

striatum

frontalcortex

substantianigra/VTA

raphe

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

/serotonin/serotonin

Vmat

transporterstimulationstimulation

DA/5HT DA/5HT

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)

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)

Drug :• cocaine• ritalin

vesicle Neuronal terminal


• Release DA from vesicles and reverse transporter

Drug Types:• Amphetamines -methamphetamine -MDMA (Ecstasy)

Vmat

transporter

serotonin/serotonin/

DA/5HT DA/5HT


00100100200200300300400400500500600600700700800800900900

1000100011001100

00 11 22 33 44 5 hr5 hr

Time After AmphetamineTime After Amphetamine

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

DADADOPACDOPACHVAHVA

AccumbensAccumbens AMPHETAMINEAMPHETAMINE

00

100100

200200

300300

400400

00 11 22 33 44 5 hr5 hrTime After CocaineTime After Cocaine

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

DADADOPACDOPACHVAHVA

AccumbensAccumbensCOCAINECOCAINE

00

100100

150150

200200

250250

00 11 22 3 hr3 hr

Time After NicotineTime After Nicotine

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

AccumbensAccumbensCaudateCaudate

NICOTINENICOTINE

Source: Di Chiara and ImperatoSource: Di Chiara and Imperato

Effects of Drugs on Dopamine ReleaseEffects of Drugs on Dopamine ReleaseEffects of Drugs on Dopamine ReleaseEffects of Drugs on Dopamine Release

100100

150150

200200

250250

00 11 22 33 4hr4hrTime After EthanolTime After Ethanol

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

0.250.250.50.5112.52.5

AccumbensAccumbens

00

Dose (g/kg ip)Dose (g/kg ip)

ETHANOLETHANOLETHANOLETHANOL

Much greaterActivity than anyOther drug of abuse -causes neurotoxicity


The Addicted BrainThe Addicted Brain

From Lecture by Leonard Howell, Emory University

CRITERIA FOR SUBSTANCE CRITERIA FOR SUBSTANCE ABUSEABUSE

A. 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.



Volkow et al. Am. J. Psychiatry 148, 621Volkow et al. Am. J. Psychiatry 148, 621

control cocaine abuser

Decreases in Metabolism in Orbito Frontal Cortex (OFC)


Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998.Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998.

(note: duration of use/3-20 yrs; abstinent/ 1-4 yrs)

METH Suppresses Expression of DAT


Comparison Subject METH AbuserComparison Subject METH Abuser

Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001.

Dopamine Transporter Loss After

Heavy Methamphetamine Use


Following Drug AddictionFollowing Drug Addiction

Ability to experience rewards is impaired.Ability to experience rewards is impaired. Commonalities in underlying Commonalities in underlying

neurobiological forces can often lead to neurobiological forces can often lead to co-morbid conditions.co-morbid conditions.– GeneticGenetic– Structural/AnatomicalStructural/Anatomical– NeurochemicalNeurochemical

Because of this overlap, drugs of abuse Because of this overlap, drugs of abuse can cause symptoms that mimic most can cause symptoms that mimic most forms of mental illness.forms of mental illness.


CommonalitiesCommonalities

Cocaine and Methamphetamine

Schizophrenia, paranoia,anhedonia, compulsivebehavior

Stimulants Anxiety, panic attacks, mania and sleep disorders

LSD, Ecstasy & psychedelics Delusions and hallucinations

Alcohol, sedatives, sleepaids & narcotics

Depression and mood disturbances

PCP & Ketamine Antisocial behavior


System Hijack!System Hijack!

Drugs of AbuseDrugs of Abuse

http://learn.genetics.utah.edu/content/addiction/drugs/mouse.html

Common Drugs of AbuseCommon Drugs of Abuse

CocaineCocaine Dopamine, Serotonin, Dopamine, Serotonin, NorepinephrineNorepinephrine

MethamphetamiMethamphetaminene

DopamineDopamine

LSDLSD SerotoninSerotonin

AlcoholAlcohol Dopamine, GABA, Serotonin, Dopamine, GABA, Serotonin, Acetylcholine, Glutamate Acetylcholine, Glutamate

HeroinHeroin GABA, Opiate ReceptorsGABA, Opiate Receptors

MarijuanaMarijuana Cannabinoid ReceptorsCannabinoid Receptors

EcstacyEcstacy Serotonin, weaker effects on Serotonin, weaker effects on Dopamine and NorepinephrineDopamine and Norepinephrine

CommercialsCommercials

Rodent Rodent Self-AdministrationSelf-Administration

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

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

David Weinshenker, PhDDavid Weinshenker, PhD

Emory UniversityEmory University

Current ResearchCurrent Research

Writing Formal Lab Writing Formal Lab ReportsReports