Addiction and the Brain
The Least You Need To Know:
•   Neurotransmitters (define)
•   reward pathway (define)
•   Old brain vs. New brain (general)
•   down-regulation (describe)
•   oops phenomenon (general)
•   drug use continuum (when addicted?)
Choice
   or
Disease?
Substance Abuse: The Nation’s
                  Number One Health iProblem
                                     ted
                                             e  in the Un
                f substa         nce abus         i cally, are
 Th  e costs o                        and phys
                  nomically                          onomically
    S tates, eco hol is the most ec                                t
                  lc  o                               s moking a
 st ag gering. A                       l lowed by
                      billion, fo                       illion, the
         at $166.5                          at $110 b
costly                 d  rug abuse he more than 2
$138 b   illion and               more, of
                                              t
                          her                               ates, one
   report   said. Furt                      e  United St
                   each        year in th             obacco an
                                                                  d
millio n deaths                          alcohol, t
                   ri butable to
   in f our is att                   drug use.
                        i l l i ci t

    Robert Wood Johnson Foundation, 2006
“Drug Addiction is a Brain
       Disease”

        Alan Leshner, PhD
  National Institute of Drug Abuse
          Former Director
The Beginning of Brain Research




                      Trepanized skulls




   1848
How the Brain Communicates
• Neurons -100 billion!—nerve cells that work
  nonstop to send and receive messages.
• Neurotransmitters—The Brain's Chemical
  Messengers that travel across the space (called the
  synapse) binds to receptors on the nearby neuron.
• Receptors—The Brain's Chemical Receivers
  A neurotransmitter and its receptor operate
  like a key and lock.
• Transporters—The Brain’s Chemical Recyclers
  Once neurotransmitters do their job, they are
  pulled back (recycling process shuts off signal)
  between the neurons.
Neurotransmitters: Chemical Messengers
Intro: Mouse Party
      -Link-
The Big Two:
• Serotonin: mood, emotion, sleep
  and appetite



• Dopamine: pleasure and elation
Many drugs work
 by mimicking a
     naturally
    occurring
neurotransmitter
   in the body.
Release of Dopamine in the Rat Nucleus
  Accumbens: Acute Administration
                      300


Dopamine (% Change)   250                        Footshock
                                                  Sucrose
                                                  Cocaine
                      200                         Nicotine
                                                  Alcohol


                      150


                      100


                       50
                            0   60   120   180     240

                                Time (min)
      Kalivas, P. 2002
OLD BRAIN VS. NEW BRAIN
Transition to Addiction
                   Good                       to                  Bad




•   Increased Energy             “It
    sustains and refreshes both body
    and brain...... in the same space of
    time more than double the amount of            Replace Natural Reward                 "A
    work could be undergone...”      Sears,        coke shot...it's like...
    Roebuck, and Co. Consumers Guide, 1900         Craving         “I found I was taking money
•   Euphoria         “.....exhilarating and        meant to buy presents for my children.”
    lasting euphoria.... You perceive
    increase in self-control and possess
                                                   Paranoia          “He thought he was
                                                   being forcibly electrocuted and could see
    more vitality and capacity for work.”
                                                   electric wires leading to his body.”
    Sigmund Freud, 1884
Oops Phenomenon
• First use to Feel Good
• Some continue to compulsively use
  because of the reinforcing effects
  – To Feel Normal
• Changes occur in the reward system
  that promote continued use.
Something truly scary….?




If you remember one thing about drugs….
National Institute on Drug Abuse, 2002; Monkey Brain
• The Pathology of Addiction (Start 3:05)
What is Down-Regulation?




National Institute on Drug Abuse, 2000
PET/fMRI of Cocaine Craving
      Childress et al., 1999; Am.J.Psychiat
‘Down’ in the Dumps
Down-Regulation
• Immediate effect of drug use is an
  increase in dopamine or NT’s
• Continued use of drugs reduces the
  brain’s dopamine (or NT) production.
• Because dopamine is part of the reward
  system, the brain is “fooled” that the
  drug has survival value for the organism.
• The reward system responds with “drug
  seeking behaviors”
Relapse or
     Recidivism


     Why 8-9
    out of 10?

    Or around
    80-90%...

Go back to using!
The face of addiction:




http://www.youtube.com/watch?v=02ngAsHRg4A
Imagine……
DRUG USE CONTINUUM

Abstinence


     Experimentation

                       Drug Use


                                  Drug
                                  Abuse


                                          Addiction
•   Deep Processing Organizer
•   Due End of Class
•   Midterm Tomorrow
•   Cumulative (1st 3 Units)
•   Review(s) Available online
Essential Questions
• So…is addiction a Choice or
  disease?
• How are depression and drug use
  related?
• How does someone become an
  ‘addict?’
http://www.youtube.com/watch?v=de
Down regulation and addiction-most updated

Down regulation and addiction-most updated

  • 1.
  • 2.
    The Least YouNeed To Know: • Neurotransmitters (define) • reward pathway (define) • Old brain vs. New brain (general) • down-regulation (describe) • oops phenomenon (general) • drug use continuum (when addicted?)
  • 3.
    Choice or Disease?
  • 4.
    Substance Abuse: TheNation’s Number One Health iProblem ted e in the Un f substa nce abus i cally, are Th e costs o and phys nomically onomically S tates, eco hol is the most ec t lc o s moking a st ag gering. A l lowed by billion, fo illion, the at $166.5 at $110 b costly d rug abuse he more than 2 $138 b illion and more, of t her ates, one report said. Furt e United St each year in th obacco an d millio n deaths alcohol, t ri butable to in f our is att drug use. i l l i ci t Robert Wood Johnson Foundation, 2006
  • 5.
    “Drug Addiction isa Brain Disease” Alan Leshner, PhD National Institute of Drug Abuse Former Director
  • 6.
    The Beginning ofBrain Research Trepanized skulls 1848
  • 8.
    How the BrainCommunicates • Neurons -100 billion!—nerve cells that work nonstop to send and receive messages. • Neurotransmitters—The Brain's Chemical Messengers that travel across the space (called the synapse) binds to receptors on the nearby neuron. • Receptors—The Brain's Chemical Receivers A neurotransmitter and its receptor operate like a key and lock. • Transporters—The Brain’s Chemical Recyclers Once neurotransmitters do their job, they are pulled back (recycling process shuts off signal) between the neurons.
  • 10.
  • 11.
  • 12.
    The Big Two: •Serotonin: mood, emotion, sleep and appetite • Dopamine: pleasure and elation
  • 13.
    Many drugs work by mimicking a naturally occurring neurotransmitter in the body.
  • 19.
    Release of Dopaminein the Rat Nucleus Accumbens: Acute Administration 300 Dopamine (% Change) 250 Footshock Sucrose Cocaine 200 Nicotine Alcohol 150 100 50 0 60 120 180 240 Time (min) Kalivas, P. 2002
  • 20.
    OLD BRAIN VS.NEW BRAIN
  • 21.
    Transition to Addiction Good to Bad • Increased Energy “It sustains and refreshes both body and brain...... in the same space of time more than double the amount of Replace Natural Reward "A work could be undergone...” Sears, coke shot...it's like... Roebuck, and Co. Consumers Guide, 1900 Craving “I found I was taking money • Euphoria “.....exhilarating and meant to buy presents for my children.” lasting euphoria.... You perceive increase in self-control and possess Paranoia “He thought he was being forcibly electrocuted and could see more vitality and capacity for work.” electric wires leading to his body.” Sigmund Freud, 1884
  • 22.
    Oops Phenomenon • Firstuse to Feel Good • Some continue to compulsively use because of the reinforcing effects – To Feel Normal • Changes occur in the reward system that promote continued use.
  • 23.
    Something truly scary….? Ifyou remember one thing about drugs….
  • 24.
    National Institute onDrug Abuse, 2002; Monkey Brain
  • 25.
    • The Pathologyof Addiction (Start 3:05)
  • 26.
    What is Down-Regulation? NationalInstitute on Drug Abuse, 2000
  • 27.
    PET/fMRI of CocaineCraving Childress et al., 1999; Am.J.Psychiat
  • 28.
    ‘Down’ in theDumps Down-Regulation • Immediate effect of drug use is an increase in dopamine or NT’s • Continued use of drugs reduces the brain’s dopamine (or NT) production. • Because dopamine is part of the reward system, the brain is “fooled” that the drug has survival value for the organism. • The reward system responds with “drug seeking behaviors”
  • 29.
    Relapse or Recidivism Why 8-9 out of 10? Or around 80-90%... Go back to using!
  • 30.
    The face ofaddiction: http://www.youtube.com/watch?v=02ngAsHRg4A
  • 31.
  • 36.
    DRUG USE CONTINUUM Abstinence Experimentation Drug Use Drug Abuse Addiction
  • 38.
    Deep Processing Organizer • Due End of Class • Midterm Tomorrow • Cumulative (1st 3 Units) • Review(s) Available online
  • 39.
    Essential Questions • So…isaddiction a Choice or disease? • How are depression and drug use related? • How does someone become an ‘addict?’
  • 40.

Editor's Notes

  • #8 Slide 2: Brain regions and neuronal pathways Certain parts of the brain govern specific functions. Point to sensory, motor, association and visual cortex to highlight specific functions. Point to the cerebellum for coordination and to the hippocampus for memory. Indicate that nerve cells or neurons travel from one area to another via pathways to send and integrate information. Show, for example, the reward pathway. Start at the ventral tegmental area (VTA) (in magenta), follow the neuron to the nucleus accumbens, and then on to prefrontal cortex. Explain that this pathway gets activated when a person receives positive reinforcement for certain behaviors ("reward"). Indicate that you will explain how this happens when a person takes an addictive drug.
  • #10 Slide 3: Neuronal Structure Remind the student that pathways are made up of neurons. Describe the anatomy of a neuron (soma, dendrites and axon are marked with text). State that this neuron is real - as viewed through a microscope. Explain the normal direction of impulse flow. Dendrites and soma receive chemical information from neighboring neuronal axons. The chemical information is converted to electrical currents which travel toward and converge on the soma. A major impulse is produced (the action potential) and travels down the axon toward the terminal. Point to the terminal.
  • #15 Slide 4: The synapse and synaptic neurotransmission Describe the synapse and the process of chemical neurotransmission. Indicate how vesicles containing a neurotransmitter, such as dopamine (the stars), move toward the presynaptic membrane as an electrical impulse arrives at the terminal. Describe the process of dopamine release (show how the vesicles fuse with the presynaptic membrane). Once inside the synaptic cleft, the dopamine can bind to specific proteins called dopamine receptors (in blue) on the membrane of a neighboring neuron. Introduce the idea that occupation of receptors by neurotransmitters causes various actions in the cell; activation or inhibition of enzymes, entry or exit of certain ions. State that you will describe how this happens in a few moments.
  • #16 Slide 5: Dopamine neurotransmission Using the close-up of a synapse, continue using dopamine for your example of synaptic function. Explain that it is synthesized in the nerve terminal and packaged in vesicles. Reiterate the steps in neurotransmission. Show how the vesicle fuses with the membrane and releases dopamine. The dopamine molecules can then bind to a dopamine receptor (in blue). After the dopamine binds, it comes off the receptor and is removed from the synaptic cleft by uptake pumps (also proteins) (in red) that reside on the terminal. This process is important so that not too much dopamine is left in the synaptic cleft at any one time. Also point out that there is a neighboring neuron, which releases another compound called a neuromodulator. In this case it is an "endorphin" (blue flying saucers). Endorphins bind to opiate receptors (in green) which reside on the post-synaptic cell or in some cases on the terminals of other neurons (this is not shown so it must be pointed out). The endorphins are destroyed by enzymes rather than removed by uptake pumps.
  • #19 Slide 10: Injection of cocaine into the nucleus accumbens Demonstrate how scientists located the structures important for the addictive nature of drugs. Show that a rat will self-administer cocaine directly into the nucleus accumbens (or the VTA) to activate the pathway. Point to an area close to the nucleus accumbens or VTA and state that if the injection is placed in this other area, the rat will not press the lever to receive the drug. Indicate that scientists know a lot more than where the drug acts to produce rewarding effects - they also know how the drugs work. Show examples with cocaine, heroin and marijuana.