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Neurosci Biobehav Rev. 2015 Sep;56:166-79. doi: 10.1016/j.neubiorev.2015.06.012. Epub 2015 Jun 24.

How fast and how often: The pharmacokinetics of drug use are decisive in addiction.

Author information

  • 1Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3C 3J7.
  • 2Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
  • 3Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3C 3J7; CNS Research Group, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3C 3J7. Electronic address: Anna.samaha@umontreal.ca.

Abstract

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.

KEYWORDS:

Cocaine; Drug addiction; Intermittent drug exposure; Pharmacokinetics; Route of drug intake; Speed of drug delivery

PMID:
26116543
DOI:
10.1016/j.neubiorev.2015.06.012
[PubMed - indexed for MEDLINE]
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