Incubation of cue-induced reinstatement of cocaine, but not sucrose, seeking in C57BL/6J mice

Alexandria L. Nugent, Ethan M. Anderson, Erin B. Larson, David W. Self

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Prior studies have shown that drug-seeking behaviors increase, rather than dissipate, over weeks to months after withdrawal from drug self-administration. This phenomenon - termed incubation - suggests that drug-craving responses elicited by conditioned environmental or discrete cues may intensify over pronged abstinence. While most of this work is conducted in rats with intravenous drug self-administration models, there is less evidence for incubation in mice that have greater utility for molecular genetic analysis and perturbation. We tested whether incubation of cocaine-seeking behavior is evident in C57BL/6J mice following 3 weeks (5 days/week) of cocaine self-administration in 2 h self-administration sessions. We compared cocaine-seeking (drug-paired lever) responses 1, 7, or 28 days after withdrawal from cocaine self-administration, and over similar times following sucrose pellet self-administration. We found that the initial re-exposure to the self-administration test chambers elicited increased reward-seeking behavior in both sucrose and cocaine self-administering mice, with maximal responses found at 7 days compared to 1 or 28 days after self-administration with either reinforcer. However, following extinction training, reinstatement of cocaine seeking reinforced by response-contingent presentation of reward-associated cues (tone/light) was significantly higher after 28 days compared to 1 or 7 days following cocaine self-administration. In contrast, cue-induced reinstatement of sucrose-paired lever pressing did not increase over this time frame, demonstrating a drug-specific incubation effect not seen with a natural reward. Thus, C57BL/6J mice display incubation of cue-induced reinstatement of cocaine seeking similar to findings with rats, but only show a transient incubation of context-induced cocaine seeking.

Original languageEnglish (US)
Pages (from-to)12-17
Number of pages6
JournalPharmacology Biochemistry and Behavior
StatePublished - Aug 2017


  • Cocaine
  • Craving
  • Cue-induced reinstatement
  • Drug-seeking
  • Extinction
  • Incubation
  • Mouse
  • Self-administration
  • Sucrose
  • Sucrose-seeking

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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