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The transition to cocaine addiction: the importance of pharmacokinetics for preclinical models


A key question in addiction research concerns how, in some individuals, initial recreational or casual patterns of drug use may change brain and psychological function in ways that promote a transition to the problematic patterns of use that define substance use disorders (addiction). In preclinical studies, this is modeled using self-administration procedures. However, most cocaine self-administration procedures produce continuously high brain concentrations of drug, whereas in people, bouts of use are thought to be more intermittent. Here, we ask whether such temporal pharmacokinetic factors matter, by comparing and contrasting the neuropsychological consequences of intermittent vs. long access cocaine self-administration experience. It turns out, the temporal pattern of cocaine use has profound effects on a number of outcomes. First, despite much less total drug consumption, intermittent access to cocaine is more effective in producing addiction-like behavior. Second, intermittent and long access cocaine self-administration change the brain in very different ways to influence motivated behavior. We argue that intermittent access self-administration procedures might be better suited than traditional self-administration procedures for isolating drug-induced changes in neuropsychological function that contribute to the transition to cocaine addiction.

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We thank David C Roberts for his generous advice on the implementation of the IntA procedure in our laboratories. We thank other members of the Robinson and Samaha laboratories who contributed to some of the studies cited here, especially Kyle Pitchers, Bryan Singer, Hajer Algallal, and Karim Bouayad-Gervais.


This study was supported by NIDA grants PO1 DA031656, RO1 DA044204 and T32 DA007281 to TER, and CIHR grant 157572 and FRQ-S salary grant 28988 to ANS.

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Correspondence to Terry E. Robinson or Anne-Noël Samaha.

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ANS is a consultant for H. Lundbeck A/S. This had no influence on the manuscript’s content. TER, ABK, and FA declare no conflicts of interest.

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Kawa, A.B., Allain, F., Robinson, T.E. et al. The transition to cocaine addiction: the importance of pharmacokinetics for preclinical models. Psychopharmacology 236, 1145–1157 (2019).

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  • Addiction
  • Preclinical
  • Self-administration
  • Cocaine
  • Dopamine
  • Intermittent access