2.7. Progressive ratio (PR)

Rats self-administered drug on a PR schedule, where the outcome measure used was the total number of infusions earned within a 6 hour session. During each daily PR session, response requirements systematically increased following each earned reinforcer in the following ratio sequence: 1, 2, 4, 6, 9, 12, 15, 20, 25, 32, 40, 50, 62, 77, 95, 118, etc., as described previously (Karkhanis et al., 2016). Cocaine doses were administered to each rat in the same pseudorandom order (0.75, 0.375, 0.19, 1.5 mg/kg/inf). Each cocaine dose was also combined with 0.03 mg/kg/inf nicotine. The pairs of cocaine-alone/cocaine+nicotine solutions at each cocaine dose were offered sequentially, with random assignment of whether cocaine-alone or cocaine-nicotine combination was offered first. No two rats received the same presentation order (for example presentation orders, see Fig. 1B). When a rat transitioned to a new dose/combination, they continued at that dose until responding was stable (three days with ≤ 20% change in total number of infusions earned) or a maximum of five days, before moving to the next dose/combination. All rats received all cocaine and cocaine + nicotine doses (8 total). The total number of days of PR responding varied between 27 and 40, depending on how quickly stable responding was reached at each dose/combination. One rat was excluded, as PR responding did not stabilize on any cocaine dose or cocaine + nicotine combination.