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Dose preference and dose escalation in extended-access cocaine self-administration in Fischer and Lewis rats

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Abstract

Rationale

Drug addiction is a disease with a genetic component that may be involved in different stages of its progression. Cocaine users escalate unit doses and frequency of self-administration events in naturalistic settings. Rats that self-administer drugs of abuse over extended sessions increase the number of infusions over days.

Objectives

Comparison of two genetically different inbred rat strains, Fischer and Lewis, in a new self-administration paradigm whereby rats select between different unit doses of cocaine, thus potentially escalating the unit dose and the number of infusions.

Methods

Extended (18 h/day) self-administration sessions lasted for 14 days. Rats had access to two active levers associated with two different unit doses of cocaine. If a rat showed preference for the higher unit dose, then the available doses were escalated in the following session. Four cocaine unit doses were available (0.2, 0.5, 1.25, and 2.5 mg/kg/infusion).

Results

Lewis rats showed a clear preference for the two higher doses of cocaine (70% of rats), with a high percentage (35%) of the individuals escalating to the highest unit dose, and escalated the total amount of cocaine taken over days. Fischer rats, however, preferred the two lower doses (63%) and did not escalate the amount of cocaine taken over days. Fischer, but not Lewis, rats showed an activated hypothalamic–pituitary–adrenal axis in acute withdrawal (24 h).

Conclusion

This work shows the power of a model of extended-access self-administration that allows for the subject-controlled dose-escalation of the unit dose of cocaine, and underlines the genetic differences that modulate cocaine intake.

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Acknowledgements

This work was supported by grants from NIH-NIDA P60-DA05130 (MJK) and The Arcadia Charitable Trust (MJK).

RP, AH, ERB, and MJK declare that, except for income received from the primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and that there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Authors and Affiliations

  1. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, Box 171, New York, NY, 10065, USA

    Roberto Picetti, Ann Ho, Eduardo R. Butelman & Mary Jeanne Kreek

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  1. Roberto Picetti
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  2. Ann Ho
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  3. Eduardo R. Butelman
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  4. Mary Jeanne Kreek
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Correspondence to Roberto Picetti.

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Picetti, R., Ho, A., Butelman, E.R. et al. Dose preference and dose escalation in extended-access cocaine self-administration in Fischer and Lewis rats. Psychopharmacology 211, 313–323 (2010). https://doi.org/10.1007/s00213-010-1899-3

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  • DOI: https://doi.org/10.1007/s00213-010-1899-3

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