Psychopharmacology

, Volume 176, Issue 1, pp 101–108

Cocaine seeking over extended withdrawal periods in rats: different time courses of responding induced by cocaine cues versus cocaine priming over the first 6 months

  • Lin Lu
  • Jeffrey W. Grimm
  • Jack Dempsey
  • Yavin Shaham
Original Investigation

DOI: 10.1007/s00213-004-1860-4

Cite this article as:
Lu, L., Grimm, J.W., Dempsey, J. et al. Psychopharmacology (2004) 176: 101. doi:10.1007/s00213-004-1860-4

Abstract

Rationale and objectives

We previously found time dependent increases, or incubation, of cocaine seeking induced by re-exposure to cocaine cues over withdrawal periods of up to 3 months. Here, we studied cocaine seeking induced by re-exposure to cocaine cues or cocaine itself over an extended withdrawal period of 6 months.

Methods

Rats were trained to self-administer intravenous cocaine for 6 h/day for 10 days. Cocaine seeking induced by re-exposure to cocaine cues or cocaine itself, as measured in extinction or drug-induced reinstatement tests, respectively, was then assessed 1 day, or 1, 3 or 6 months after withdrawal. Rats were first given six 1-h extinction sessions wherein lever presses resulted in contingent presentations of cues previously paired with cocaine infusions. Subsequently, reinstatement of drug seeking induced by cocaine injections (expt 1: 0, 5, and 15 mg/kg, IP; expt 2: 0, 2.5, and 5 mg/kg) was assessed during three 1-h sessions.

Results

Profound time dependent changes in responsiveness to cocaine cues in the extinction tests were observed, with low responding after 1 day, high responding after 1 and 3 months, and intermediate responding after 6 months of withdrawal. In contrast, no significant time dependent changes in cocaine-induced drug seeking were found; acute re-exposure to cocaine effectively reinstated responding at all withdrawal periods.

Conclusions

Results indicate that the withdrawal period is a critical modulator of drug seeking provoked by re-exposure to cocaine cues, but not cocaine itself. Results also indicate that while the incubation of responsiveness to cocaine cues is a long lasting phenomenon, it is not permanent.

Keywords

Craving Cocaine cues Extinction Priming Reinstatement Relapse Self-administration Withdrawal 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Lin Lu
    • 1
  • Jeffrey W. Grimm
    • 1
    • 2
  • Jack Dempsey
    • 1
  • Yavin Shaham
    • 1
  1. 1.Behavioral Neuroscience BranchIRP/NIDA/NIH/DHHSBaltimoreUSA
  2. 2.Department of PsychologyWestern Washington UniversityBellinghamUSA