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Self-administration of D9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys

Self-administration of D9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys

  1. NeuroChi
    Interest in therapeutic activities of
    cannabinoids has been restrained by the fact that they are
    most often mediated through activation of cannabinoid
    CB1 receptors, the same receptors that mediate the effects
    of D9-tetrahydrocannabinol (THC) and are responsible for
    the abuse liability of marijuana. Persistent intravenous
    self-administration of THC by animals was first demonstrated
    in squirrel monkeys and shown to be mediated by
    CB1 receptors, but monkeys in the study had a history of
    cocaine self-administration, raising the possibility that
    persistent neurobiological adaptations might subsequently
    predispose animals to self-administer THC. Objectives: To
    demonstrate persistent intravenous self-administration of
    THC in drug-naive squirrel monkeys. Methods: Monkeys
    with no history of exposure to other drugs learned to press
    a lever for intravenous injections (0.2 ml in 0.2 s) of THC
    under a 10-response, fixed-ratio schedule with a 60-s
    time-out after each injection. Acquisition of THC selfadministration
    was rapid and the final schedule was
    reached in 11–34 sessions. Dose of THC was then varied
    from 1 to 16 mg/kg per injection with vehicle extinction
    following each dose of THC. Results: THC maintained
    significantly higher numbers of self-administered injections
    per session and higher rates of responding than
    vehicle at doses of 2, 4 and 8 mg/kg per injection, with
    maximal rates of responding at 4 mg/kg per injection.
    Response rates, injections per session and total THC
    intake per session were two- to three-fold greater in
    monkeys with no history of exposure to other drugs
    compared to previous findings in monkeys with a history
    of cocaine self-administration. Conclusions: THC can act
    as an effective reinforcer of drug-taking behavior in
    monkeys with no history of exposure to other drugs,
    suggesting that self-administration of THC by monkeys
    provides a reliable animal model of human marijuana
    abuse.