Abstract(s)
How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the
addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which
we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and
of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature
demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal
models of addiction. This literature includes recent data highlighting the importance of intermittent, ‘spiking’ brain levels of drug in
producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push
the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better
understanding the neuroadaptations that are critical for the disorder.