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. 2014 Jan;348(1):174–191. doi: 10.1124/jpet.113.208264

TABLE 5.

Statistical analyses of effects of pretreatments on the self-administration of d-methamphetamine, heroin, ketamine, and remifentanil substitution for heroin as shown in Figs. 2–6.

Treatment Self-Administered Drug Dose (i.v.) Treatment Dose (i.p.) Interaction Post Hoc Tests
WIN35,428 pretreatments (i.p.)
 d-Methamphetamine self-administration F4,60 = 5.29; P = 0.005 F3,60 = 7.40; P = 0.003 F12,60 = 9.77; P < 0.001 1.0 mg/kg (i.p.) at EXT, t = 9.11, P < 0.001
 Heroin self-administration F4,60 = 24.9; P < 0.001 F3,60 = 17.7; P < 0.001 F12,60 = 20.4; P < 0.001 0.32 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 8.65, P < 0.001
1.0 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 12.6, P < 0.001
0.32 mg/kg (i.p.) at 3.2 µg/kg/inj, t = 3.52, P = 0.005
0.32 mg/kg (i.p.) at 10 µg/kg/inj, t = 3.44, P = 0.006
1.0 mg/kg (i.p.) at 10 µg/kg/inj, t = 3.71, P = 0.002
 Ketamine self-administration F4,60 = 11.3; P < 0.001 F3,60 = 9.17; P = 0.001 F12,60 = 8.75; P < 0.001 1.0 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 5.07, P < 0.001
0.32 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 4.25, P < 0.001
0.32 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 4.20, P < 0.001
1.0 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 5.45, P < 0.001
d-Amphetamine pretreatments (i.p.)
 d-Methamphetamine self-administration F3,60 = 4.43; P = 0.010 F3,60 = 6.83; P = 0.004 F12,60 = 8.75; P < 0.001 1.0 mg/kg (i.p.) at EXT, t = 8.60, P < 0.001
 Heroin self-administration F4,60 = 24.6; P < 0.001 F3,60 = 5.41; P = 0.010 F12,60 = 22.6; P < 0.001 0.32 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 8.18, P < 0.001
1.0 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 11.9, P < 0.001
0.32 mg/kg (i.p.) at 10 µg/kg/inj, t = 5.03, P < 0.001
1.0 mg/kg (i.p.) at 10 µg/kg/inj, t = 7.13, P < 0.001
1.0 mg/kg (i.p.) at 32 µg/kg/inj, t = 3.18, P = 0.013
 Ketamine self-administration F4,60 = 11.2; P < 0.001 F3,60 = 9.18; P = 0.001 F12,60 = 7.97; P < 0.001 1.0 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 5.85, P < 0.001
0.32 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 4.70, P < 0.001
0.32 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 3.07, P = 0.019
1.0 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 4.63, P < 0.001
JHW007 pretreatments (i.p.)
 d-Methamphetamine self-administration F4,60 = 29.5; P < 0.001 F3,60 = 20.7; P < 0.001 F12,60 = 18.8; P < 0.001 3.2 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 5.61, P < 0.001
10 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 7.39, P < 0.001
3.2 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 8.91, P < 0.001
10 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 12.0, P < 0.001
 Heroin self-administration F4,60 = 30.7; P < 0.001 F3,60 = 0.771; P = 0.528 F12,60 = 1.75; P = 0.078 3.2 mg/kg (i.p.) at 32 µg/kg/inj, t = 3.95, P = 0.001
 Ketamine self-administration F4,60 = 12.1; P < 0.001 F3,60 = 5.35; P = 0.001 F12,60 = 4.99; P < 0.001 1.0 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 7.28, P < 0.001
3.2 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 5.46, P < 0.001
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 7.67, P < 0.001
AHN2-005 pretreatments (i.p.)
 d-methamphetamine self-administration F4,60 = 20.0; P < 0.001 F3,60 = 15.4; P < 0.001 F12,60 = 10.3; P < 0.001 3.2 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 2.76, P = 0.046
10 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 6.20, P < 0.001
3.2 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 4.25, P < 0.001
10 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 9.73, P < 0.001
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 3.11, P = 0.017
 Heroin self-administration F4,60 = 28.4; P < 0.001 F3,60 = 0.131; P = 0.940 F12,60 = 1.32; P = 0.234 NS (versus vehicle, i.p.)
 Ketamine self-administration F4,60 = 11.7; P < 0.001 F3,60 = 3.64; P = 0.038 F12,60 = 4.11; P < 0.001 1.0 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 4.25, P < 0.001,
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 6.37, P < 0.001
AHN1-055 pretreatments (i.p.)
 d-Methamphetamine self-administration F4,60 = 6.29; P = 0.002 F3,60 = 9.97; P < 0.001 F12,60 = 11.6; P < 0.001 3.2 mg/kg (i.p.) at EXT, t = 9.35, P < 0.001
3.2 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 3.37, P = 0.007
10 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 3.09, P = 0.017
 Heroin self-administration F4,60 = 26.6; P < 0.001 F3,60 = 1.55; P = 0.243 F12,60 = 2.43; P = 0.013 1.0 mg/kg (i.p.) at 10 µg/kg/inj, t = 3.08, P = 0.019
 Ketamine self-administration F4,60 = 11.5; P < 0.001 F3,60 = 8.58; P = 0.001 F12,60 = 5.82; P < 0.001 3.2 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 3.34, P = 0.008
3.2 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 6.76, P < 0.001
dl-Methadone pretreatment (i.p.)
 Heroin self-administration F4,60 = 29.2; P < 0.001 F3,60 = 25.4; P < 0.001 F12,60 = 8.22; P < 0.001 1.0 mg/kg (i.p.) at 3.2 µg/kg/inj, t = 3.99, P < 0.001
3.2 mg/kg (i.p.) at 3.2 µg/kg/inj, t = 6.20, P < 0.001
1.0 mg/kg (i.p.) at 10 µg/kg/inj, t = 5.69, P < 0.001
3.2 mg/kg (i.p.) at 10 µg/kg/inj, t = 9.17, P < 0.001
10 mg/kg (i.p.) at 32 µg/kg/inj, t = 3.78, P = 0.002
 Remifentanil self-administration F4,60 = 12.1; P < 0.001 F3,60 = 7.60; P = 0.003 F12,60 = 5.27; P < 0.001 3.2 mg/kg (i.p.) at 0.32 µg/kg/inj, t = 3.25, P = 0.011
10 mg/kg (i.p.) at 0.32 µg/kg/inj, t = 4.94, P < 0.001
1.0 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 2.86, P = 0.035
3.2 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 5.20, P < 0.001
10 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 7.40, P < 0.001
 d-Methamphetamine self-administration F4,60 = 35.3; P < 0.001 F3,60 = 0.895; P = 0.467 F12,60 = 3.12; P = 0.002 10 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 2.88, P = 0.036
 Ketamine self-administration F4,60 = 11.2; P < 0.001 F3,60 = 6.63; P = 0.005 F12,60 = 5.79; P < 0.001 1.0 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 5.84, P < 0.001
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 7.42, P < 0.001
Morphine pretreatments (i.p.)
 Heroin self-administration F4,60 = 29.1; P < 0.001 F3,60 = 23.4; P < 0.001 F12,60 = 26.1; P < 0.001 3.2 mg/kg (i.p.) at 3.2 µg/kg/inj, t = 6.74, P < 0.001
10 mg/kg (i.p.) at 3.2 µg/kg/inj, t = 7.79, P < 0.001
3.2 mg/kg (i.p.) at 10 µg/kg/inj, t = 8.33, P < 0.001
10 mg/kg (i.p.) at 10 µg/kg/inj, t = 12.0, P < 0.001
10 mg/kg (i.p.) at 32 µg/kg/inj, t = 4.40, P < 0.001
 Remifentanil self-administration F4,60 = 5.62; P = 0.003 F3,60 = 6.83; P = 0.004 F12,60 = 5.27; P < 0.001 3.2 mg/kg (i.p.) at 0.32 µg/kg/inj, t = 3.39, P = 0.007
10 mg/kg (i.p.) at 0.32 µg/kg/inj, t = 4.70, P < 0.001
3.2 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 4.27, P < 0.001
10 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 7.03, P < 0.001
 Ketamine self-administration F4,60 = 8.92; P < 0.001 F3,60 = 4.74; P = 0.016 F12,60 = 4.53; P < 0.001 1.0 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 6.35, P < 0.001
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 3.92, P = 0.001
 d-Methamphetamine self-administration F4,60 = 29.0; P < 0.001 F3,60 = 1.10; P = 0.381 F12,60 = 2.09; P = 0.031 1.0 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 3.06, P = 0.019
(+)-MK-801 pretreatments (i.p.)
 Ketamine self-administration F4,60 = 10.8; P < 0.001 F3,60 = 7.92; P = 0.002 F12,60 = 9.50; P < 0.001 0.1 mg/kg (i.p.) at EXT, t = 3.07, P = 0.019
0.1 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 5.71, P < 0.001
0.032 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 3.18, P = 0.014
0.032 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 5.69, P < 0.001
0.1 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 4.27, P < 0.001
 d-Methamphetamine self-administration F4,60 = 27.7; P < 0.001 F3,60 = 9.42; P < 0.001 F12,60 = 24.8; P < 0.001 0.032 mg/kg (i.p.) at 0.01 mg/kg/inj, t = 5.67, P < 0.001
0.1 mg/kg (i.p.) at 0.01 mg/kg/inj, t = 9.86, P < 0.001
0.01 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 3.38, P = 0.007
0.032 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 3.71, P = 0.002
0.032 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 5.07, P < 0.001
0.1 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 9.05, P < 0.001
 Heroin self-administration F4,60 = 27.4; P < 0.001 F3,60 = 11.1; P < 0.001 F12,60 = 1.44; P = 0.175 NS (vs. vehicle, i.p.)
 Remifentanil self-administration F4,20 = 5.39; P = 0.004 F1,20 = 9.12; P = 0.029 F4,20 = 7.01; P = 0.001 0.1 mg/kg (i.p.) at 0.32 µg/kg/inj, t = 5.06, P < 0.001
0.1 mg/kg (i.p.) at 1.0 µg/kg/inj, t = 3.62, P = 0.002
Memantine pretreatments (i.p.)
 Ketamine self-administration F4,60 = 12.5; P < 0.001 F3,60 = 12.2; P < 0.001 F12,60 = 10.5; P < 0.001 10 mg/kg (i.p.) at EXT, t = 3.97, P = 0.001
3.2 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 3.12, P = 0.016
10 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 7.01, P < 0.001
3.2 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 3.32, P = 0.009
3.2 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 5.01, P < 0.001
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 6.18, P < 0.001
 Heroin self-administration F4,60 = 7.36; P < 0.001 F3,60 = 4.95; P = 0.014 F12,60 = 3.92; P < 0.001 1.0 mg/kg (i.p.) at 3.2 µg/kg/inj, t = 4.03, P < 0.001
1.0 mg/kg (i.p.) at 10 µg/kg/inj, t = 5.16, P < 0.001
 Remifentanil self-administration F4,20 = 4.54; P = 0.009 F1,20 = 0.797; P = 0.413 F4,20 = 0.789; P = 0.546 NS (vs. vehicle, i.p.)
0.1 mg/kg WIN35,428 and BD1008 pretreatments (i.p.)
 d-Methamphetamine self-administration in rats trained with d-methamphetamine F4,100 = 28.5; P < 0.001 F5,100 = 34.5; P < 0.001 F20,100 = 22.2; P < 0.001 3.2 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 6.42, P < 0.001
10 mg/kg (i.p.) at 0.032 mg/kg/inj, t = 8.38, P < 0.001
3.2 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 9.57, P < 0.001
10 mg/kg (i.p.) at 0.10 mg/kg/inj, t = 13.4, P < 0.001
10 mg/kg (i.p.) at 0.32 mg/kg/inj, t = 3.47, P = 0.011
 Heroin self-administration in rats trained with heroin F4,20 = 30.0; P < 0.001 F1,20 = 7.11; P = 0.045 F4,20 = 1.72; P = 0.185 NS (vs. vehicle, i.p.)
 Ketamine self-administration in rats trained with ketamine F4,20 = 11.2; P < 0.001 F1,20 = 2.59; P = 0.169 F4,20 = 4.02; P = 0.015 NS (vs. vehicle, i.p.)

NS, not statistically significant; inj, injection.