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Drugsandthe Brain Part2 Addiction
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Drugsandthe Brain Part2 Addiction

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  • 1. Drugs and the Brain Part 2 Addiction
  • 2. Addiction
    • Compulsive, drug craving, seeking, and use that persists even in the face of negative consequences.
    • 3 components:
      • Tolerance, dependence, & compulsive drug-seeking behavior
    • Most addictions are rooted in the reward pathway
    • Tolerance & dependence have a chemical basis; compulsive drug seeking may be a sociological phenomenon
  • 3. Tolerance
    • Tolerance = a state in which an organism no longer responds to a drug
    • Higher dose is required to achieve same effect.
      • Thus, the effect of a given dose is diminished.
    • Tolerance is not addiction
      • Tolerance can develop to drugs that are not addictive
    • Can be produced by several different mechanisms
    • Chronic overstimulation of the reward pathway causes a homeostatic response
      • Dopamine reward system is down regulated
    • Metabolic tolerance takes place in the liver.
      • Chronic exposure stimulates enzymes in the liver to degrade the drug more rapidly.
  • 4. Dependence
    • A state in which the organism functions normally only in the presence of the drug
    • Manifests as physical disturbance when the drug is removed (withdrawal)
    • Withdrawal symptoms are usually the opposite of the drug’s effect
  • 5. Dependence & the Brain
    • The development of dependence also involves specific areas of the brain.
    • These are separate from the reward pathway.
    • The thalamus and brainstem are key areas in dependence.
  • 6. The Reward Pathway
    • The reward pathway plays a key role in addiction.
    • This pathway involves: the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex.
    • When activated by a rewarding stimulus (e.g, food, water, sex), information travels from the VTA to the nucleus accumbens and then up to the prefrontal cortex.
    • The neurons of the VTA contain dopamine which is released in the nucleus accumbens and in the prefrontal cortex.
  • 7. The Reward Pathway Pictured
  • 8. Understanding the Reward Pathway
    • Research in rats led to understanding of the reward pathway
    • Rats were trained to press a lever for a tiny electrical jolt to certain parts of the brain.
    • When an electrode is placed in the nucleus accumbens, the rat keeps pressing the lever to receive the electrical stimulus
      • This stimulation is interpreted as pleasure
      • Positive reinforcement.
      • When the electrode is placed near, but not in, the nucleus accumbens, the rat will not press the lever because it does not activate the reward pathway.
  • 9. Reward Pathway Research
    • Activation of the reward pathway by an electrical stimulus.
  • 10. Drugs Act in Different Parts of the Pathway
    • Heroin & nicotine act on the VTA
      • Dopamine neurons from the VTA project through the lateral hypothalamus to the forebrain
      • These dopaminergic neurons have both opiate and nicotinic acetylcholine receptors.
    • Cocaine acts on the nucleus accumbens
      • The nucleus accumbens is a target of the ascending dopaminergic axons in the forebrain
  • 11. Rat Experiments Using Drugs to Stimulate the Reward Pathway
  • 12. The Role of Dopamine
    • Scientists can measure an increased release of dopamine in the reward pathway after the rat receives the reward.
    • If the dopamine release is prevented (either with a drug or by destroying the pathway), the rat won't press the bar for the electrical jolt.
  • 13. Dopamine is the Link in Addiction
    • Addictive drugs are biochemically quite different
      • Activate different neurotransmitter systems
      • Produce different psychoactive effects
      • Heroin acts on the opiate system
      • Nicotine acts on the cholinergic system
      • Cocaine acts on dopaminergic & noradrenergic systems
    • All either stimulate dopamine release (heroin, nicotine) or enhance dopamine action (cocaine) in the nucleus accumbens.
    • Animals are motivated to perform behaviors that stimulate dopamine release in the nucleus accumbens & related structures
  • 14. Measuring Brain Activity - PET
    • Position Emission Tomography (PET) measures emissions from radio-labeled chemicals (F 18 -deoxyglucose and/or a labeled drug) injected into the bloodstream.
    • Shows which areas of the brain are more or less active by measuring the amount of glucose used by different brain regions.
      • Glucose is the main energy source for the brain.
      • When brain regions are more active, they will use more glucose and when they are less active they will use less.
    • The data is used to produce images of the distribution of the chemicals in the body.
  • 15. Measuring Brain Activity
  • 16. PET Scans & Drug Research
    • PET scans can be used to identify brain sites where drugs and naturally occurring neurotransmitters act.
    • Can show how quickly drugs reach and activate receptors and how long they occupy these receptors.
    • PET is also used to show brain changes following chronic drug abuse, during withdrawal from drug use, and during the experience of drug craving.
    • PET can be used to assess the effects of pharmacological and behavioral therapies for drug addiction on the brain.
  • 17. Interpreting a PET Scan
    • The left scan is taken from a normal, awake subject.
    • The red color shows the highest level of glucose utilization (yellow represents less utilization and blue the least).
    • The right scan is taken from a subject on cocaine.
    • The loss of red areas in the right scan compared to the left (normal) scan indicates that the brain is using less glucose and therefore is less active.
  • 18. PET Scan of Brain Activity on Cocaine
  • 19. Long Term Effects of Addiction
    • Once addicted, the brain is changed.  
    • PET scan shows the level of brain function
      • Yellow indicates greatest activity
    • Top row = normal brain.
      • Yellow indicates high brain activity
    • Middle row shows a cocaine addict’s brain after 10 days without any cocaine.
      • Less yellow = less activity occurring in the brain.
    • Third row shows the same addict’s brain after 100 days without any cocaine.
      • A little more yellow, but the addict’s brain is not back to a normal level of functioning 
  • 20.  
  • 21. Memory of Drugs
    • PET scan demonstrates how just the mention of items associated with drug use may cause an addict to “crave” or desire drugs.
    • Study compared recovering addicts, who had stopped using cocaine, with people who had no history of cocaine use.
    • Goal was to determine what parts of the brain are activated when drugs are craved.
  • 22.  

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