Lecture 2: Substance Use

    Cards (19)

    • Cocaine blocks reuptake transporters, increasing the amount of dopamine in the synapse.
    • Animals will lever press to receive intravenous infusions of most drugs abused by humans (esp. cocaine, amphetamine, heroin, nicotine, but not LSD, THC?)
    • Rats will self-administer cocaine until death (90%),
      Heroin ‘less’ toxic at 36% deaths
    • Cocaine is rewarding at it causes an increase in dopamine levels in the brain (blocks the dopamine transporter “endocytosis”)
    • Rewarding effect of cocaine is blocked by: Dopamine receptor antagonists
    • What is the problem with dopamine receptor antagonists as a treatment for addiction?
      Compliance
    • Several lines of evidence suggest that craving involves increased glutamate release (from prefrontal cortex to nucleus accumbens)
    • What are the two regions of the brain that have strong glutamate projections to the nucleus accumbens, causing craving?
      The amygdala and anterior cingulate
    • Glutamate is involved with learned associations with the drug-taking environment
    • Glutamate in the nucleus accumbens triggers craving in abstinent individuals.
      Future treatments may involve specific glutamate receptor antagonists or agents that normalise glutamate levels
    • NAC regulates glutamate levels
    • Acamprosate = glutamate NMDA receptor antagonist
    • Bupropion = dopamine reuptake inhibitor
    • Varenicline is a nicotine receptor partial agonist
    • Nicobrevin contains camphor, eucalyptus oil, Menthyl valerate, and quinine.
    • Clonidine
      • agonist at alpha2- adrenoceptors (noradrenaline)• helps to reduce withdrawal effects of opioids, cocaine and nicotine
      • noradrenaline cell bodies in the locus coeruleus are thought to produce withdrawal symptoms
      • not widely used - intolerable side effects (low blood pressure, drowsy)
    • Psychostimulant replacement therapy (benztropines)?
      • Similar to methadone but aimed at blocking the dopamine transporter
      • Prevents cocaine from having it’s effect at the DAT
      • Drugs bind slowly to DAT and stay there for a long time
    • Oxytocin may be effective in treating which two substance use disorders?
      Alcohol and methampethamine
    • Medicinal cannabis may be effective for methamphetamine addiction.
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