Table 5.

Plasma exposure levels for amphetamine, methylphenidate, nicotine, and atomoxetine at timepoints relevant to the tests.

		Plasma concentration (ng/ml)
		0.5 h	1 h	2 h
d-Amphetamine	0.03 mg/kg	8 ± 2	5 ± 1	3 ± 1
	0.1 mg/kg	35 ± 5	25 ± 5	18 ± 6
	0.3 mg/kg	97 ± 20	55 ± 12	29 ± 5
	0.6 mg/kg	250 ± 23	135 ± 23	80 ± 20
	1 mg/kg	29 ± 9	20 ± 5	11 ± 1
Methylphenidate	3 mg/kg	113 ± 59	120 ± 55	50 ± 15
	6 mg/kg	220 ± 100	160 ± 60	70 ± 30
	10 mg/kg	600 ± 250	320 ± 150	216 ± 100
	0.05 mg/kg	9 ± 1	7 ± 1	3 ± 1
Nicotine	0.1 mg/kg	15 ± 1	14 ± 2	6 ± 1
	0.2 mg/kg	37 ± 2	27 ± 1	13 ± 1
	0.4 mg/kg	60 ± 6	63 ± 18	21 ± 2
	0.1 mg/kg	3 ± 1	2 ± 1	1 ± 1
Atomoxetine	0.5 mg/kg	12 ± 2	12 ± 1	6 ± 1
	1 mg/kg	23 ± 9	15 ± 4	9 ± 6
	2 mg/kg	35 ± 9	31 ± 19	24 ± 16

Both d-Amphetamine and nicotine were administered 10 min before test, and methylphenidate and atomoxetine administered 30 min before test. The timepoints of 0.5, 1, and 2 h refer to exposure levels at these stages of test session. The duration of test sessions ranged from 0.25–0.5h (progressive ratio test), to 0.5–0.45 h (usITI, sSD, Go-NoGo tests), to 1 h (long ITI 5-CSRTT). For comparison, plasma levels of d-Amphetamine, methylphenidate, nicotine, and atomoxetine reported in humans are: d-amphetamine (30–80 ng/ml; see Adderall XR Product Monograph), methylphenidate (5–20 ng/ml; see Swanson and Volkow, 2001; Storebø et al., 2015), nicotine (10–50 ng/ml; Russell et al., 1975; Matta et al., 2007), and atomoxetine (Hazell et al., 2009). Thus, there is good translation between plasma levels in rats and humans based on therapeutic effects for both d-amphetamine and nicotine. Some differences may be evident for both methylphenidate and atomoxetine, both of which also seemed to show a wider interanimal variability in terms of exposure compared to d-amphetamine and nicotine.