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Drug dependence (addiction mechanism (Physical dependence (Adaptation…

- - - - Peer pressure
      - Unemployment
      - Childhood abuse
      - Formulation
      - mode of delivery
    - - Personality traits
        
        Impulse control
        
        Risk-taking
      - Drug disposition
        
        Pharmacokinetics
        
        Pharmacodynamics
      - Psychopathology
        
        Anxiety
        
        Depression
        
        Personality disorder
      - Stress responsivity
      - Drug induced neurochemical changes
  - - - oppioids, alcohol, cannabis
        
        work on inhibitory GABA neurons that
        project to DA neurons in VTA
      - Nicotine
        
        works on nAChRs at the DA neurons in VTA
      - Mesolimbic (reward) pathway
        
        DA neurons of the VTA projecting to the nucleus Accumbens
      - Cocaine & MDMA
        
        work through blocking the uptake or increaseing
        release of DA from presynaptic terminall
    - - reinforcing the positive behaviours
        
        Sex
        
        Food
    - - Intracranial stimulation in the VTA causes pleasure
      - D2 antagonists prevent that effect
      - Knock-out models
  - - - Receptor upregulation
      - increased NT synthesis
      - increased 2nd messenger concentrations
      - more depolarisations
      - Plasticity
    - - Withdrawal symptoms are the opposite
        of acute effects of the drug
      - Caused by disrupted balance of inhibition/excitation (more excitation) in the absence of the drug
      - Heroin withdrawal
        
        Withdrawal effects
        
        Aches and pains
        
        Spontaneous muscle contractions (reflexes)
        
        Tears, runny nose
        
        Fever, goosebumps
        
        Diarrhea
        
        Coughing
        
        Panicky
        
        Acute effects
        
        Reflexes down
        
        Secretions down
        
        Feeling of warmth
        
        Constipation
        
        Cough down
        
        Anxiety down
        
        Pain relief
    - - effects mediated through the opioid receptors
        in the forebrain, midrain and spinal cord
    - - effects mediated through Ca2+ channels, GABARs and many other targets
      - very severe withdrawals
    - - association component
        
        environment of the same friends or places, which were associated with drug abuse promotes the relapse
- - - - Recreational
      - Socially controlled
      - culturally conscious lifestyle
      - clubs, home use
    - - addicted
      - Injecting
      - social and economic deprivation
      - inner city, street use