Saline-1.0 mg/kg SKF 83959 0.02 mg/kg SCH 23390-Vehicle
0.02 mg/kg SCH 23390-1.0 mg/kg SKF 83959
*** ***
Saline-1.0 mg/kg SKF 83959 0.06 mg/kg SCH 23390-Vehicle
0.06 mg/kg SCH 23390-1.0 mg/kg SKF 83959
** ***
Figure 22.The DRL 10-s response-based indexes after SCH 23390 pretreatment (n = 9): 0.02 mg/kg SCH 23390 (A, B, C, D) and 0.06 mg/kg SCH 23390 (E, F, G, H).Neither doses of SCH 23390 reversed the effects of SKF
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Figure 23.The DRL 10-s peak rate, peak time, and MRE after SCH 23390 pretreatment (n = 9):
0.02 mg/kg SCH 23390 (A, B, C) and 0.06 mg/kg SCH 23390 (D, E, F).Neither doses of SCH 23390 reversed the SKF 83959-induced decline in peak rates. The drug treatments did not affect the peak time.* p < 0.05; ** p < 0.01; *** p < 0.001 in comparison to respective vehicle. (Exp.4)
Saline-1.0 mg/kg SKF 83959 0.02 mg/kg SCH 23390-Vehicle
0.02 mg/kg SCH 23390-1.0 mg/kg SKF 83959
**
Saline-1.0 mg/kg SKF 83959 0.02 mg/kg SCH 23390-Vehicle
0.02 mg/kg SCH 23390-1.0 mg/kg SKF 83959
**
Saline-1.0 mg/kg SKF 83959 0.06 mg/kg SCH 23390-Vehicle
0.06 mg/kg SCH 23390-1.0 mg/kg SKF 83959
** **
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0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
Bin (3-Sec)
0.06 mg/kg Eticlopride-1.0 mg/kg SKF 83959
A
B
Figure 24.The FI 30-s IRT curve after eticlopride pretreatment in a within-subjects design (n = 9): 0.02 mg/kg eticlopride (A) and 0.06 mg/kg eticlopride (B) Low dose eticlopride appeared to partially reverse the SKF 83959-induced decline in response frequency on the FI 30-s schedule, while high dose
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Figure 25.The FI 30-s indexes after eticlopride pretreatment (n = 9): 0.02 mg/kg eticlopride (A, B, C) and 0.06 mg/kg eticlopride (D, E, F). Low dose eticlopride had a partial reversal effect on the SKF 83959-induced decline in total response rate on the FI 30-s schedule. * p < 0.05; ** p <
0.01 relative to vehicle. (Exp.4)
R e in fo rc e d R e s p o n s e
Saline-1.0 mg/kg SKF 83959 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
**
Saline-1.0 mg/kg SKF 83959 0.06 mg/kg Eticlopride-Vehicle
0.06 mg/kg Eticlopride-1.0 mg/kg SKF 83959
*
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Saline-1.0 mg/kg SKF 83959 0.06 mg/kg Eticlopride-Vehicle
0.06 mg/kg Eticlopride-1.0 mg/kg SKF 83959 2D Graph 1
Saline-1.0 mg/kg SKF 83959 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
A
B
Figure 26. The DRL 10-s IRT curve after eticlopride pretreatment in a within-subjects design (n = 8):
0.02 mg/kg eticlopride (A) and 0.06 mg/kg eticlopride (B). Low dose eticlopride appeared to partially reverse the SKF 83959-induced decline in response frequency on the DRL 10-s schedule, while high
‧
Saline-1.0 mg/kg SKF 83959 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
*
Saline-1.0 mg/kg SKF 83959 0.06 mg/kg Eticlopride-Vehicle
0.06 mg/kg Eticlopride-1.0 mg/kg SKF 83959
***
Figure 27.The DRL 10-s response-based indexes after eticlopride pretreatment (n = 8): 0.02 mg/kg
eticlopride (A, B, C, D) and 0.06 mg/kg eticlopride (E, F, G, H). Low dose eticlopride had a partial reversal effect on the SKF 83959-induced declines in response rates on the DRL 10-s schedule. High dose eticlopride
A
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Saline-1.0 mg/kg SKF 83959 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
**
Saline-1.0 mg/kg SKF 83959 0.06 mg/kg Eticlopride-Vehicle
0.06 mg/kg Eticlopride-1.0 mg/kg SKF 83959
**
Figure 28. The DRL 10-s peak rate, peak time, and MRE after eticlopride pretreatment (n = 8): 0.02 mg/kg eticlopride (A, B, C) and 0.06 mg/kg eticlopride (D, E, F). Low dose eticlopride had a partial reversal effect on the SKF 83959-induced decline in peak rate. High dose eticlopride did not have such a reversal effect. ** p < 0.01; *** p < 0.001 in comparison to the respective vehicle. (Exp.4)
A
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Bin (3-Sec)
0 1 2 3 4 5 6 7 8 9 10
Fr equenc y
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
Saline-Saline-Vehicle
Saline-Saline-1.0 mg/kg SKF 83959
0.02 mg/kg SCH 23390+0.02mg/kg Eticlopride-Vehicle
0.02 mg/kg SCH 23390+0.02mg/kg Eticlopride-1.0 mg/kg SKF 83959
Figure 29.The FI 30-s IRT curve after the combined administration of 0.02 mg/kg SCH 23390 and 0.02 mg/kg eticlopride in a within-subjects design (n = 9). The co-administration of SCH 23390 and eticlopride did not reverse the SKF 83959-induced decline in response frequency on the FI 30-s schedule. (Exp.4)
‧
0.02 mg/kg SCH 23390 + 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg SCH 23390 + 0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
Figure 30. The FI 30-s indexes after the combined administration of 0.02 mg/kg SCH 23390 and 0.02 mg/kg eticlopride (n = 9): total response (A), reinforced response (B), and PRP (C). The co-administration of SCH 23390 and eticlopride did not reverse the effects of SKF 83959-on the FI 30-s indexes. ** p <
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Bin (Sec)
0 5 10 15 20
F re q u e n c y
0 5 10 15 20 25 30 35 40
Saline-Vehicle
Saline-1.0 mg/kg SKF 83959
0.02 mg/kg SCH 23390+0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg SCH 23390+0.02 mg/kg Eticlopride-1.0mg/kg SKF 83959
Figure 31.The DRL 10-s IRT curve after the combined administration of 0.02 mg/kg SCH 23390 and 0.02 mg/kg eticlopride in a within-subjects design (n = 8). (Exp.4)
‧
0.02 mg/kg SCH 23390 + 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg SCH 23390 + 0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
Figure 32.The DRL 10-s reponse-based indexes after the combined administration of 0.02 mg/kg SCH 23390 and 0.02 mg/kg eticlopride (n = 8). The co-administration of SCH 23390 and eticlopride did not reverse the SKF 83959-induced declines in response rates. ** p < 0.01; *** p < 0.001 in comparison to respective vehicle.
‧
Saline-Saline-1.0 mg/kg SKF 83959
0.02 mg/kg SCH 23390 + 0.02 mg/kg Eticlopride-Vehicle
0.02 mg/kg SCH 23390 + 0.02 mg/kg Eticlopride-1.0 mg/kg SKF 83959
Figure 33. The DRL 10-s peak rate (A), peak time (B), and MRE (C) after the combined administration of 0.02 mg/kg SCH 23390 and 0.02 mg/kg eticlopride (n = 8). The co-administration of SCH 23390 and eticlopride did not reverse the SKF 83959-induced decline in peak rate on the DRL 10-s schedule.
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Appendix
A List of Abbreviated Words
Adenylyl cyclase (AC)
Calcium and calmodulin-dependent protein kinase II (CaMKII)
Cyclic adenosine monophosphate (cAMP)
Cyclic AMP response element binding protein (CREB)
Differential reinforcement of low rate (DRL)
Dopamine (DA)
Dopamine and cyclic AMP-regulated phosphoprotein, 32 KDa (DARPP-32)
Dopamine receptor (DAR)
Dorsal striatum (DS)
Extracellular signal regulated kinase (ERK)
Fixed interval (FI)
Fixed ratio (FR)
Guanosine-5’-triphosphate (GTP)
Human embryonic kidney cells (HEK cells)
Intracranial self-stimulation (ICSS)
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Inter-response time (IRT)
Medial forebrain bundle (MFB)
Modified response efficiency (MRE)
Norepinephrine (NE)
Nucleus accumbens (NAc)
Phosphorylated CaMKII (pCaMKII)
Phosphorylated CREB (pCREB)
Phosphorylated ERK (pERK)
Phosphoinositide (PI)
Phospholipase C (PLC)
Prefrontal cortex (PFC)
Protein kinase A (PKA)
Post-reinforcement pause (PRP)
Total response (TR)