Drugs & Rewards

• Brain rewards pathway


  Substantia Nigra, VTA, Nucleus accumbens, prefrontal cortex
• Electrical Stimulation in Rats (Olds & Milner, 1954)


  1. Electrodes placed in different brain areas

  2. Deliver stimulation when lever is pressed

  3. Certain areas inspired non-stop lever pressing

  4. These are now considered the "rewards pathway"
• Brain imaging during habit learning (Wickens and others, 1990 etc.)

  Substantia nigra (dopamine production area) is active when monkeys receive a reward
• Dopamine


  The messenger in this reward circuit
• Electrical Stimulation in Humans (Heath 1964)

  Pleasurable emotion when septal area is stimulated
• Rewards


  • Give a pleasurable sensation or reduce an unpleasant sensation
  • Pleasure is the nervous system's way of saying something is worth doing again
• Addictive drugs


  Production / release of dopamine in the nucleus accumbens
• Addiction


  • Developing tolerance
  • Withdrawal symptoms
  • Overwhelming involvement
• Opponent Processes


  • Nervous system compensates for drug by doing something opposite
  • Often outlasts the original effect
• Mechanisms of Addiction


  1. Dopamine rewards increase desire for repeated use

  2. Desensitization: Body compensates by reacting less to the same dose

  3. Decreased production: Body compensates by producing less

  4. Withdrawal symptoms provide punishment for ending use
• Caffeine


  • Binds to adenosine receptors and prevents reception
  • Adenosine signals drowsiness, dilates blood vessels in brain
  • Caffeine also blocks enzyme involved in inhibiting stress reaction of the endocrine system
  • Caffeine is also a dopamine re-uptake inhibitor
• Nicotine


  • Excites Acetylcholine (ACh) receptors in the CNS, as if it were the NT
  • ACh helps to direct attention in the pre-frontal and parietal cortex
  • Excites neurons in the ventral tegmental area (VTA), which signal for dopamine release in the nucleus accumbens

  
• Cocaine


  • Prevents transmitting synaptic vesicle from grabbing NT back
  • Most active on dopamine, so dopamine persists longer in synapse
  • Side effects include anxiety and hallucinations
  • Desensitization results in addiction

  
• Amphetamines


  • Stimulate the release of dopamine, serotonin, and norepinephrine
  • Also inhibit the enzyme (monoamine oxidase) that breaks them down
  • Also block reuptake, and stimulate receptors
  • Net effect: lots more dopamine activity

  
• Methamphetamine


  As above only faster and more powerful
• Adderall, Ritalin, etc.


  • Amphetamines that release slowly
  • Used properly, these improve attentional focus, but do not give the short-term boost in dopamine associated with rewards and addiction
• Alcohol


  • Has inhibitory effects on CNS, by affecting receptors for GABA and Glutamate
  • Net effect: inhibiting inhibitory signals from cortex
  • Also inhibits enzyme that breaks down dopamine, signaling reward
  • Paradoxical effects: stimulation while BAC is rising, depressant while BAC is falling

  
• Benzodiazepines (e.g. Valium, Xanax, Ativan)


  Have similar effect on GABA as alcohol
• Opiates


  • Mimic the effects of endorphins
  • Block transmission of pain signals (substance P)
  • Poppy derived opiates: opium, codeine, morphine, heroin
  • Synthetic opioids: oxycodone, Percocet, Vicodin, hydrocodone, Fentanyl, etc.
• LSD


  Targets serotonin receptors
• Prozac (and other SSRIs)


  Block serotonin reuptake, almost exclusively
• Marijuana


  • Active ingredient is THC which targets cannabinoid receptors
  • Found in VTA, the hippocampus, hypothalamus, cerebellum and more
  • Happy, stupid, hungry and clumsy
• Ecstasy


  • Stimulates serotonin release and blocks reuptake
  • Also norepinephrine and dopamine
  • Interferes with body temperature regulation, leads to serotonin depletion, "black Mondays"
• many drugs of abuse—such as opioids, cocaine, or nicotine—cause dopamine to flood the reward pathway, 10 times more than a natural reward. The brain remembers this surge and associates it with the addictive substance.