Limited versus extended cocaine intravenous self-administration: Behavioral effects and electrophysiological changes in insular cortex

CNS Neurosci Ther. 2021 Feb;27(2):196-205. doi: 10.1111/cns.13469. Epub 2020 Oct 29.


Aims: Limited vs extended drug exposure has been proposed as one of the key factors in determining the risk of relapse, which is the primary characteristic of addiction behaviors. The current studies were designed to explore the related behavioral effects and neuronal alterations in the insular cortex (IC), an important brain region involved in addiction.

Methods: Experiments started with rats at the age of 35 days, a typical adolescent stage when initial drug exposure occurs often in humans. The drug-seeking/taking behaviors, and membrane properties and intrinsic excitability of IC pyramidal neurons were measured on withdrawal day (WD) 1 and WD 45-48 after limited vs extended cocaine intravenous self-administration (IVSA).

Results: We found higher cocaine-taking behaviors at the late withdrawal period after limited vs extended cocaine IVSA. We also found minor but significant effects of limited but not extended cocaine exposure on the kinetics and amplitude of action potentials on WD 45, in IC pyramidal neurons.

Conclusion: Our results indicate potential high risks of relapse in young rats with limited but not extended drug exposure, although the adaptations detected in the IC may not be sufficient to explain the neural changes of higher drug-taking behaviors induced by limited cocaine IVSA.

Keywords: cocaine; drug seeking; drug taking; insula cortex; whole-cell patch-clamp.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Administration, Intravenous* / methods
  • Animals
  • Cocaine / administration & dosage*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Drug Administration Schedule
  • Drug-Seeking Behavior / drug effects*
  • Drug-Seeking Behavior / physiology
  • Insular Cortex / drug effects*
  • Insular Cortex / physiology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration


  • Dopamine Uptake Inhibitors
  • Cocaine