Drugsandthe Brain Part2 Addiction


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Drugsandthe Brain Part2 Addiction

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