Taking Rapid and Intermittent Cocaine Infusions Enhances Both Incentive Motivation for the Drug and Cocaine-induced Gene Regulation in Corticostriatal Regions

Neuroscience. 2020 Aug 21:442:314-328. doi: 10.1016/j.neuroscience.2020.05.058. Epub 2020 Jul 15.


A goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug self-administration are essential in this context. Here, we compared in male rats two cocaine self-administration procedures that differ in the extent to which they evoke addiction-like behaviours. We measured both incentive motivation for cocaine using progressive ratio procedures, and cocaine-induced c-fos mRNA expression, a marker of neuronal activity. Rats self-administered intravenous cocaine (0.25 mg/kg/infusion) for seven daily 6-hour sessions. One group had intermittent access (IntA; 6 minutes ON, 26 min OFF × 12) to rapid infusions (delivered over 5 s). This models the temporal kinetics of human cocaine use and produces robust addiction-like behaviour. The other group had Long access (LgA) to slower infusions (90 s). This produces high levels of intake without promoting robust addiction-like behaviour. LgA-90 s rats took twice as much cocaine as IntA-5 s rats did, but IntA-5 s rats showed greater incentive motivation for the drug. Following a final self-administration session, we quantified c-fos mRNA expression in corticostriatal regions. Compared to LgA-90 s rats, IntA-5 s rats had more cocaine-induced c-fos mRNA in the orbitofrontal and prelimbic cortices and the caudate-putamen. Thus, a cocaine self-administration procedure (intermittent intake of rapid infusions) that promotes increased incentive motivation for the drug also enhances cocaine-induced gene regulation in corticostriatal regions. This suggests that increased drug-induced recruitment of these regions could contribute to the neural and behavioural plasticity underlying the transition to addiction.

Keywords: cocaine self-administration; immediate early gene; incentive motivation; intermittent access; long access.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine*
  • Cocaine-Related Disorders*
  • Dopamine Uptake Inhibitors
  • Male
  • Motivation
  • Pharmaceutical Preparations*
  • Rats
  • Self Administration


  • Dopamine Uptake Inhibitors
  • Pharmaceutical Preparations
  • Cocaine

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