A–C: Shown are the mean ± SEM catecholamine levels expressed as a percentage of baseline (±SEM) values in 16-minute microdialysis samples collected before (negative numbers) and after (positive numbers) injection of vehicle (VEH) or MPH. Clinically-relevant doses of MPH administered orally (A; 2.0 mg/kg) or intraperitoneally (B; 0.5 mg/kg) elicited large increases in extracellular dopamine (DA) within the PFC relative that that seen in the nucleus accumbens (NAcc). (C) Similarly, for norepinephrine (NE), intraperitoneal administration of 0.5 mg/kg MPH elicited a large increase in extracellular NE in the PFC with little change in the medial septal area (MSA). For both DA and NE, although clinically relevant doses of MPH elicit smaller effects outside the PFC, these effects are nonetheless statistically significant relative to both baseline and vehicle-treated animals. D: Bars represent effects of 0.5 mg/kg MPH intraperitoneally expressed as a % change from vehicle-treated animals (mean ±SEM) for DA and NE over a 30-minute period beginning at 15-minutes post-treatment. When measured in this manner, although MPH increases NE and DA outside the PFC by ~30% this effect was not significantly significant. *P<0.05, **P <0.01 compared with vehicle-treated animals. #P<0.01 relative to PFC DA. From (24).