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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

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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.

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Acknowledgements

We thank Polly Robarts, Shirley Liu and Kelly Badger for technical assistance.

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Author notes

  1. Jeffrey W. Grimm

    Present address: Department of Psychology, Western Washington University, 516 High Street, Bellingham, WA 98225-9089, USA

Authors and Affiliations

  1. Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA

    Lin Lu, Jeffrey W. Grimm, Jack Dempsey & Yavin Shaham

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  1. Lin Lu
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  2. Jeffrey W. Grimm
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Correspondence to Yavin Shaham.

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Lu, L., Grimm, J.W., Dempsey, J. et al. 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. Psychopharmacology 176, 101–108 (2004). https://doi.org/10.1007/s00213-004-1860-4

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  • DOI: https://doi.org/10.1007/s00213-004-1860-4

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