Regulation of cocaine self-administration in humans: lack of evidence for loading and maintenance phases

Background: In rodents, cocaine self-administration under a fixed-ratio schedule and with timeout intervals limited to the duration of the infusions is characterized by an initial burst of drug intake (loading) followed by more stable infusion rates (maintenance). We sought to examine whether similar phases might characterize self-regulated cocaine use in humans.

Methods: 31 Non-treatment seeking, cocaine dependent subjects participated in three (8, 16, and 32 mg/70 kg/infusion), self-regulated, 2-h cocaine self-administration sessions under a fixed-ratio 1, 5-min timeout schedule. Data were assessed for visual (e.g., by graphs of cumulative numbers of infusions) and statistical evidence of change in phase (by step-function analyses of individual infusion rates).

Results: Graphs of cumulative infusions over time suggested a single, linear rate of self-administration over 2h at each cocaine dose. Statistical analyses of infusion data by generalized estimating equation (GEE) models also failed to support a loading/maintenance pattern (suggesting, if anything, the possibility of increasing infusion rates over time).

Conclusions: Our findings fail to support the existence of distinct loading and maintenance phases of self-regulated cocaine administration in humans at behaviorally relevant doses. Several factors may account for these observations including differences between humans and rodents in self-regulated drug intake.