Cocaine self-administration training

Six male Sprague Dawley rats (from Harlan, Indianapolis, IN, initial weight 180–200 g and 400–500 g over the duration of the studies) were housed individually on a 12/12 h light/dark cycle (lights on at 6:00 a.m.) and food and water were available ad lib. Herein we present results obtained from the same experiment as in our previous publication⁸ but the data set was differently analyzed.

Indwelling catheters were surgically implanted into the right jugular vein under halothane anesthesia. Beginning five or seven days after the surgery, rats were trained to self-administer cocaine HCl using the FR1 schedule with a time-out (TO) period equal to the injection duration but not shorter than 5 s. The house light in the chamber was turned on during the time of pump activation (5–40 s) signaling TO. Training at the unit dose of 1.5 μmol/kg (0.51 mg/kg) cocaine continued until individual rats met the criterion of stable maintained self-administration. This criterion was no significant change of the mean and standard deviation of the inter-injection intervals between five consecutive sessions. At the same time the proportion of inactive lever presses was lower than 2.5% of the total presses.

Cocaine unit doses were controlled by the duration of pump activation. After self-administration of the initial priming (programmed escalating doses until initiation of self-administration or 2–4 doses fixed at 1.5 μmol/kg) and loading phases of the session, the program allowed self-administration of 50 doses of 0.3 μmol/kg under FR1 and then switched to PR schedule delivering one of the following doses: 0.75, 1.5, 3.0, 6.0 or 12.0 μmol/kg. These doses were selected in pseudo random fashion between sessions. Every cocaine unit dose was repeated 5 times totaling 150 sessions from 6 rats. Data from 24 sessions were excluded from analyses because animals did not show normal patterns of self-administration (6 sessions), due to technical errors (3 sessions) or because BPs in first 1–2 sessions under the PR schedule were substantially lower than after that (15 sessions). Results of all individual sessions before exclusions can be found in ^{Supplementary Materials}.

The total number of injections at each cocaine dose delivered during self-administration sessions maintained under the FR1 schedule was preset to keep the total duration of self-administration between 2 and 3 h. Sessions were aborted any time after the first inter-press interval longer than 30 min. This criterion is consistent with the conventional 1 h since the last drug delivery, as lever-pressing activity during extinction was observed for approximately 30 min.