FIGURE 1.

The experimental design for animal assignment and drug administration. (A) A blinded crossover design was used to randomly assign rats to treatment groups (Group A: saline first; Group B: d-amphetamine first). After experiment 1, the rats received a 1-week rest period and then received the opposite treatment (d-amphetamine or saline). Final datasets for behavioral or arterial blood gas analysis were only included if animals completed the entire protocol. (B) A timeline showing the protocol for an individual experiment. Fentanyl (55 µg/kg, IV) was administered over 15 min and then d-amphetamine (3 mg/kg, IV) or saline (vehicle) was administered over 2 min. There was 1 min between fentanyl and d-amphetamine infusions to allow for the exchange of drug lines. Arterial blood was drawn for blood gas analysis before the experiment (baseline), 1 min before the end of the fentanyl infusion (t = −2) and 5, 15 and 60 min from the start of the d-amphetamine infusion. All behavioral and blood gas time points were referenced to the start of the d-amphetamine or saline infusion (t = 0).