Drugs, Addiction, and Reward

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CHAPTER 5

• Drugs, Addiction, and Reward
• Addiction

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Addiction

• Societal definition not a scientific definition
• obsession, compulsion, or excessive physical
  dependence or psychological dependence
• E.g., drug addiction, alcoholism, compulsive
  overeating, problem gambling, computer addiction,
  pornography, etc.

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Addiction

• Scientific definition of Addiction A state in
  which
• Physical dependence the body relies on a
  substance for normal functioning and develops
• Withdrawal When the drug or substance on which
  someone is dependent is suddenly removed,
  physical symptoms occur.
• Drug tolerance. More and more of the drug is
  required to achieve the same effect
• However, common usage spread to include
  psychological dependence, but brain doesnt
  recognize this distinction

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Addiction

• Addiction and withdrawal take place in different
  parts of the brain and are independent of each
  other.
• The ventral tegmental area is suggested to be
  involved in addiction
• Periventricular gray area produces classic signs
  of withdrawal.

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Addiction

• Not mean that addicts never take drugs to avoid
  withdrawal symptoms
• E.g., one type of alcoholism is avoidance of
  painful experiences via alcohol
• Means that withdrawal is not necessary for
  addiction and avoidance of withdrawal is not an
  explanation of addiction.

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Addiction pathways
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Addiction involves Dopaminergic pathway

• mesolimbicortical dopamine system
• Major reward system
• Many drugs (especially stimulants) mimic effects
  of normal reward.
• begins in the midbrain (mesencephalon) and
  projects to the limbic system and prefrontal
  cortex.
• The most important structures in the system
• nucleus accumbens
• medial forebrain bundle
• ventral tegmental area.

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Dopaminergic Reward pathways

• Reward
• Defined by your book positive effect an object
  or condition such as a drug, food, sexual
  contact, and warmth has on the user
• Dopamine serves as a feedback signal do that
  behavior again, you got something!
• General Reward System
• Food- and thus any behaviors related to feeding
• Water- and thus any behaviors related to drinking
• Sex- and thus any behaviors related to sex
  (including maternal)
• Drugs and drug related behavior

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Reward and the Dopaminergic pathway

• Schultz (2005) and others show
• Dopamine is not released as a reward
• Dopamine is a motivating neurotransmitter-
  produces increases in locomotion, action behavior
  that is oriented towards reward
• Thus when dopamine released, body moves towards
  or continues doing whatever it was doing to keep
  getting that Reward
• General DA reward system serves as feedback
  system that identifies
• need to continue or shift behavior depending on
  reward situation
• Helps select the appropriate response for the
  situation

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Changing behavior with DA agonists

• Virtually all the abused drugs increase dopamine
  levels in the nucleus accumbens.
• Electrical stimulation of the brain (ESB),
• Stimulate Nucleus accumbens
• Animals press a level or engage in high rates of
  locomotion immediately after receiving
  stimulation
• Why? DA release elicits search behavior
• A reinforcer is any object or event that
  increases the probability of the response that
  precedes it
• Thus, must keep doing the behavior that got you
  the reinforcer
• DA maintains ongoing responses or kicks you into
  movement behaviors that increase likelihood of
  reward.

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Changing behavior with DA agonists

• Think of symptoms of stimulant abuse/addiction
• Lots of motor movement
• Lots of perseverative motor behavior
• Nose wiping
• Tics
• Perseveration
• Paranoia is highly similar to schizophrenia
• Why? Too much dopamine is overstimulating
  circuits, cognitive areas of brain are
  hyperstimulated.
• What got you these feelings- the drug
• What do to keep these feelings- get more drug
• And, because you have replaced normal DA levels,
  now you will engage in seeking behaviors to
  maintain those levels!

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Diminished dopamine?

• Chronic drug users show diminished DA release
  from DA receptors
• May be individual, and not the addiction
• Lower levels of D2 autoreceptors
• Note that those with high number of D2
  autoreceptors find DA drugs unpleasurable those
  with fewer report more pleasure
• D2 autoreceptors help regulate general DA tone in
  synapse, regulate reuptake and production of DA
• Thus, may be that DA-drug addicts have reward
  deficiency syndrome insufficient receptors to
  respond to DA, need more DA to get same effect

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Addiction learning

• Addiction learning
• Learning produces changes in the brain
• Addiction produces same changes
• Specifically Step down reflex and compensation

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Step down reflex

• Drug release of DA
• US(drug)? UR(drug effects)
• Stimulus (CS) predicts drug that releases DA
• CS(cue? US(drug)? UR(drug effects)

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Step down reflex

• Anticipate of reward ? DA release
• BUT Body prefers homeostasis no sudden changes,
  maintain level
• CS(cue? US(drug)? UR(drug effects)
• \
• ?CR(decrease DA release in anticipation of drug
  DA release)
• Thus body REDUCES dopamine in ANTICIPATION of
  increase in DA

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Compensation tolerance and withdrawal

• Body REDUCES dopamine in ANTICIPATION of increase
  in DA
• No longer get same effect for drug
• Must take more
• This is called tolerance
• If stop taking the drug, no step-down reflex or
  compensation
• Now, reduction in DA in anticipation, but no DA
  comes
• Now have too little DA shaky, motor tremors,
  etc.
• This is called withdrawal Setting cues are
  critically important

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PET scans are shown at two depths in the brain.
Notice the increased activity during presentation
of cocaine-related stimuli. Frontal areas (DL,
MO) and temporal areas (TL, PH) are involved in
learning and emotion.
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Evidence for Addiction?

• Nora Volkow, et al.s work how do people
  transition from controlled drug use to compulsive
  drug intake
• Found that it involves pathological changes in
  communication between prefrontal cortex and the
  nucleus accumbens.
• addict returns to drug taking when stress or
  drug-related stimuli trigger increases in
  dopamine release in the prefrontal cortex and
  glutamate release in the nucleus accumbens.
• Prefrontal release produces a compulsive focus on
  drugs at the expense of other reinforcers
• Glutamate release cranks up the drive to engage
  in drug seeking.

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Treating Addiction

• Agonist treatments replace an addicting drug with
  another drug that has a similar effect.
• Opiate addiction is often treated with a
  synthetic opiate called methadone.
• Antagonist treatments involve drugs that block
  the effects of the addicting drugs.
• Drugs that block opiate receptors are used to
  treat opiate addictions and alcoholism because
  they reduce the pleasurable effects of the drug.
• Antabuse for alcohol
• Another experimental strategy is to interfere
  with the dopamine reward system.
• Baclofen reduces dopamine activity in the ventral
  tegmental area by activating GABAB receptors on
  dopaminergic neurons.

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The two rats received the same amount of alcohol,
but the one on the right received a drug that
blocks the effect of alcohol at the GABAA receptor
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TREATMENT OF Addiction

• Aversive treatments cause a negative reaction
  when the person takes the drug.
• Antabuse interferes with alcohol metabolism, so
  drinking alcohol makes the person ill.
• Antidrug vaccines are synthetic molecules that
  resemble the drug but have been modified to
  stimulate the animals immune system to make
  antibodies that will degrade the drug.

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The Role of Genes in Addiction

• If genetics plays such an important role in
  addiction, just what is inherited?
• Most research on the genetics of addiction
  implicates various neurotransmitter systems.
• Appears to be a syndrome or related group of
  dysfunction
• Addicts correlated with individuals who have
  family members with
• Schizophrenia, bipolar disorder, depression
• ADHD and related disorders
• Autism and autism-spectrum disorders.

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The Role of Genes in Addiction

• Dopamine is one of the factors differentiating
  addictive from normal behavior.
• There are several alleles, or alternate forms, or
  the gene responsible for the development of the
  D2 subtype of dopamine receptor.
• Various alleles are associated with alcoholism,
  cocaine dependence, stimulant abuse, and multiple
  addictions.

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The Role of Genes in Addiction

• Serotonin is involved in drug abuse in general
• Also in mood,
• sexual behavior,
• aggression,
• the regulation of bodily rhythms and food and
  water intake.
• Bottom line May have a predisposition
• Stress bring out or turns on different coping
  mechanism
• Best way to avoid reduce stress avoid
  situations with drug availability

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A Societal comment on drug usage from the onion!

• And now for something absolutely silly!
• http//www.theonion.com/content/video/fda_approves
  _depressant_drug_for