Chapter 5

• Addiction (DSMIV)


  1. impaired control over use of drug, b) use has harmful consequences
• Why do we self-administer?

  • Lack of spiritual strength or sin (handled by church)
  • 19th century social reform, alcoholics not responsible
  • 20th century, physicians use morphine, drug abuse becomes medical problem
• Disease Model


  • "addiction" becomes synonymous with excessive drug abuse an addiction is a sickness or disease
  • excessive drug use is a result of a disease condition, i.e., some abnormal biochemical or neurological state
• Physical Dependence Model


  • excessive drug use is motivated by the fear of withdrawal symptoms
  • addiction became synonymous with dependence
  • psychological dependence
• Reinforcement Model


  • animals will self-administer low doses of drugs that do not produce physical dependence
  • drugs act as positive reinforcers (any stimulus that increases the frequency of a behaviour – not necessarily pleasure)
• Paradox: people/animals continue to use drugs even when drug use leads to aversive consequences
• Monkeys with free access to cocaine and amphetamine will refuse to eat and sleep, self-inflict wounds, and die from an overdose or from sustained injury, all the while continuing to use the drugs
• Reinforcing value or incentive value


  Factors Influencing Reinforcing Value
• Factors Influencing Reinforcing Value

  • drug dose – larger doses are usually more reinforcing
  • genetic – different breeds or strains of mice bred to avoid/abuse alcohol
  • task demand – coloured pills, chose psychomotor stimulant for vigilance tasks and benzodiazepine for relaxation task
  • relief of unpleasant symptoms
  • stress – increases incentive value of drugs
  • deprivation – hungry or thirsty animals will self-administer more alcohol or cocaine (stress?)
  • previous history with other or same drug
  • physical dependence can increase reinforcement strength
  • extended access (cocaine access for 1hr, versus 6hr: 1hr group stabilized amount over 12 days, 6hr group didn't)
  • priming – press bar to get cocaine, then extinguish (press bar no cocaine), then introduce cocaine (noncontingent), start to press bar again
• Conditioned reinforcement


  • place conditioning
  • second order schedules
  • sensitization, craving, priming
• Motivational Control System


  • three interconnected systems: reinforcement, learning/memory, motor
  • reinforcement (mesolimbic, VTA – nucleus accumbens) system activated with 'deficiency' stimulus (e.g. hunger)
  • motor loop: activation of reinforcement system removes inhibition of motor system (basal ganglia) which engages motor behaviour
  • both of these systems responsible for activation
• Neural Basis of Reinforcement

  • motor behaviour is directed by memory system (hippocampus/amygdala) and its interpretation of sensory input with respect to past experiences (memory determines incentive salience of stimuli) – necessary for guidance
  • in turn (full circle), sight of a stimulus with high incentive salience causes stimulation of mesolimbic which then encourages more movement

  
• Reinforcement ≠ Pleasure
• Nucleus accumbens originally labelled the "pleasure center"
• Reinforcement


  • Stimuli can act as reinforcers without the sensation of pleasure
  • MLS is most active in response to stimuli that precede consumption, not during consumption itself (which would seem to be the source of pleasure)
  • MLS function seems to be related to "wanting" or repeating actions, not "liking"
  • MLS has 2 roles related to wanting: general activation and direct behaviour towards particular goal (incentive salience)
  • nucleus accumbens assigns incentive value to stimuli associated with natural reinforcers
• Drugs as Reinforcers


  • most/(all?) drugs known to be positive reinforcers stimulate the accumbens
  • lesioning the MLS stops self-administration of drugs in animals
  • food ('natural' reinforcer) activates MLS when hungry, not when satiated – drugs have no built in satiation signal
• Stress


  • stress hormones stimulate dopamine in the n. accumbens and intensify the effect of drugs
  • exposure to stress can sensitize the n. accumbens and make drugs more reinforcing
• Incentive Sensitization Theory of Addiction

  • mesolimbic dopamine becomes sensitized due to repeated exposure to the drug
  • this leads to increased incentive salience of drug and related stimuli -- and increased "wanting", i.e., "craving"
  • ERP studies show increased processing of heroin-related stimuli in ex heroin users
  • even moderate social users of alcohol and marijuana are faster to detect changes in drug-related items in a picture of various items
• Disruption of Brain Control Circuits

  • A dysfunction in information processing and integration amongst multiple brain regions
  • Circuits that regulate "reward/saliency" (MLS) – down-regulation on D2 receptors
  • Circuits that regulate "motivation/drive" (e.g., orbitofrontal cortex and anterior cingulate gyrus) – deficit in metabolism and grey matter
  • Circuits that regulate "inhibitory control/executive function" (e.g., prefrontal cortex) – deficit in metabolism and grey matter