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Variability of drug self-administration in rats

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Abstract

Rationale

Although temporal patterns of drug self-administration in animals are known to be highly regular, this regularity has rarely been quantified or systematically compared across reinforcers.

Objectives

Over a range of unit doses, this study assessed: (1) the within-subject variability of inter-infusion intervals (latencies); (2) the estimated whole-body drug level at the time of self-infusion; (3) the within-subject variability of these drug levels; and (4) the statistical dependence between successive latencies, to determine whether regularity is maintained by compensatory, moment-to-moment adjustment of latencies.

Methods

Rats were trained with cocaine (10–1000 μg/kg per infusion, IV), remifentanil (an ultra-short acting opioid; 0.25–32 μg/kg per infusion, IV), or food (20–180 mg/delivery).

Results

Within subjects, latencies were most consistent from infusion to infusion at unit doses on the descending limb of the dose-response curve. However, the drug level at the time an infusion was initiated was actually least consistent at these doses. Sequential latencies showed only a weak autocorrelation for both drugs.

Conclusion

These results suggest that highly consistent response patterns are not simply a product of precise titration of drug levels. The weak autocorrelation between sequential latencies suggests that temporal regularity of responding is not maintained through compensatory adjustments of post-infusion pauses.

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Acknowledgements

We are grateful to Eric Thorndike and Bettye Campbell for technical assistance, Linda Felch and David Epstein for assisting with statistical analysis, and Edward Cone for assisting with analysis of drug levels. Preliminary reports of this research were presented at the meetings of the College on Problems of Drug Dependence in 2000 and the Society for Neuroscience in 2001. This study was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH,DHHS.

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Authors and Affiliations

  1. Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA

    Leigh V. Panlilio & Charles W. Schindler

  2. Medication Discovery Research Branch, NIDA/NIH/DHHS, Baltimore, MD 21224, USA

    Jonathan L. Katz

  3. Associate Vice President For Research, Virginia Commonwealth University, Richmond, VA 23298, USA

    Roy W. Pickens

Authors
  1. Leigh V. Panlilio
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  2. Jonathan L. Katz
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  3. Roy W. Pickens
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  4. Charles W. Schindler
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Correspondence to Leigh V. Panlilio.

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Panlilio, L.V., Katz, J.L., Pickens, R.W. et al. Variability of drug self-administration in rats. Psychopharmacology 167, 9–19 (2003). https://doi.org/10.1007/s00213-002-1366-x

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  • DOI: https://doi.org/10.1007/s00213-002-1366-x

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