Characterization of cocaine self-administration and pharmacokinetics as a function of time of day in the rat.

Two experiments examined the influence of time of day on the intravenous self-administration of cocaine and its associated pharmacokinetic profile in male Sprague-Dawley rats. In both experiments, individual rats were randomly assigned to experimental groups (n = 6/group) according to four selected times of day, 0100, 0700, 1300, and 1900 h, during which experimental procedures were conducted. In both experiments, rats were maintained under a 12 L:12 D ambient lighting cycle, with lights on at 0600 h. Training and testing was thus conducted either 1 (0700, 1900) or 7 (1300, 0100 h) hours into the light and dark phases. In Experiment 1, characteristics of cocaine self-administration across a behaviorally active dose range were assessed. Statistically significant differences were observed in the rates and patterns of self-administration across the four experimental groups, most notably characterized by an apparent shift in the dose of cocaine, which engendered peak rates of responding. Specifically, groups tested at 0100 and 1300 h appeared to exhibit enhanced sensitivity to the reinforcing properties of low-dose cocaine relative to groups tested at 0700 and 1900 h. The observed differences in apparent sensitivity of experimental subjects to low-dose cocaine were not related in any simple way to ongoing patterns of general locomotor activity, and were not accompanied by corresponding variance in the pharmacokinetic profiles of cocaine when assessed over 1 h following an intravenous infusion (1.8 mg/kg) at each of the four sampling periods noted above.