Isradipine and compound 8 promote extinction of cocaine/ethanol CPP and prevent future reinstatement. (a and b) Summary graphs depicting the effects of systemic isradipine administration (i.p.) on the expression and extinction of CPP previously induced with cocaine (a) or ethanol (b) (three conditioning sessions for both). A single injection of isradipine (1.2 mg/kg) or vehicle [1 ml/kg of 16% ethanol (0.13 g/kg)] was made prior to the second posttest, while cocaine/ethanol injections were made immediately before the fifth and seventh posttests to trigger reinstatement (2-week interval between fifth and sixth posttests) [(a) F7,126 = 3.40, p < 0.001, n = 10 rats/group; (b) F7,91 = 3.21, p < 0.01, n = 7–8 rats/group; mixed two-way ANOVA). (c and d) Summary graphs showing the effects of intra-VTA injection of isradipine (c) or compound 8 (d) made before the second posttest following cocaine CPP acquisition. Cocaine-induced reinstatement was tested on the fifth posttest [(c) F5,80 = 13.82, p < 0.001, n = 9 rats/group; (d) F5,70 = 9.62, p < 0.001, n = 7–9 rats/group; mixed two-way ANOVA). (e) Intra-VTA isradipine injection had no effect when done immediately after the second posttest (F3,42 = 0.45, p = 0.72, n = 7–9 rats/group; mixed two-way ANOVA). (f) Systemic isradipine injection (i.p.) followed by intra-VTA injection of AP5 or vehicle was made before the second posttest (F3,30 = 9.71, p < 0.001, n = 6 rats/group; mixed two-way ANOVA). *p < 0.05, **p < 0.01, ***p < 0.001 vs. pretest; +p < 0.05, +++p < 0.001 between two successive posttests; #p < 0.05, ##p < 0.01, ###p < 0.001 between groups (Bonferroni post hoc test).