Journal
PSYCHOPHARMACOLOGY
Volume 167, Issue 1, Pages 9-19Publisher
SPRINGER
DOI: 10.1007/s00213-002-1366-x
Keywords
titration; regulation; cocaine; remifentanil; food
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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 mug/kg per infusion, IV), remifentanil (an ultra-short acting opioid; 0.25-32 mug/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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