Fig. 4.

Effect of substituting cocaine, SB-277011A or saline for cocaine in animals proficient at maintaining cocaine self-administration behaviour. (A) Time-courses of cocaine, SB-277011A or saline self-administration behaviour by 20-min intervals. Two-way ANOVA for repeated measures revealed a statistically significant difference between cocaine (0.5 mg/kg/infusion) self-administration behaviour and SB-277011A (1.25 mg/kg/infusion) self-administration behaviour, and between cocaine self-administration behaviour and saline (0.08 mL/infusion) self-administration behaviour. However, there were no significant differences between SB-277011A self-administration behaviour and saline self-administration behaviour at any time point tested. *P < 0.05, ***P < 0.001, individual group comparisons, when compared with cocaine self-administration group at each time point marked. (B) Mean numbers of drug infusions summed over the 3-h test session for cocaine (0.5 mg/kg/infusion), SB-277011A (1.25 mg/kg/infusion) or saline (0.08 mL/infusion) self-administration behaviour. Both the extinction-like pattern of responding (A) and the cumulative 3-h reduction in self-administration behaviour (B) after substitution of SB-277011A suggest that SB-277011A itself has no reinforcing effect at the test dose of 1.25 mg/kg/infusion. ***P < 0.001, individual group comparisons, when compared with cocaine self-administration group. SA, self-administration; SB, SB-277011A.