期刊
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
卷 56, 期 -, 页码 166-179出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2015.06.012
关键词
Drug addiction; Pharmacokinetics; Cocaine; Route of drug intake; Speed of drug delivery; Intermittent drug exposure
资金
- Fonds de la Recherche en Sante du Quebec [28988, 29651]
How much, how often and how fast a drug reaches the brain determine the behavioural and neuro-plastic 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. (C) 2015 Elsevier Ltd. All rights reserved.
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