Figure 3. Cocaine-induced single trial behavioral sensitization is accompanied by increased stimulation of NAC core, but not NAC shell, DA transmission, which is blocked by antagonism at CB1 receptors.

The figure shows the time course of the effects of systemic administration of cocaine 10 mg/kg (top panels, A, C), or 20 mg/kg (lower panels, B,D) on extracellular levels of DA in dialysates from the NAC core (left panels) or shell (right panels) in control animals (● filled circles, number of mice and basal levels of extracellular DA expressed as femtomoles/10-μl sample ± S.E.M. were: n=5, 41.1 ± 3.9, and n=5, 42.9 ± 4.9 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the core; n=6, 57.9 ± 6.7 fmoles/sample, and n=9, 48.4 ± 4.7 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the shell), or in animals sensitized to cocaine (○ unfilled circles, n=7, 37.4 ± 2.0 fmoles/sample, and n=6, 30 ± 3.4 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the core; n=9, 48.5 ± 3.0 fmoles/sample, and n=8, 51.3 ± 4.2 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the shell), in animals pretreated with RIM 1 mg/kg and cocaine 20 mg/kg (◻ unfilled squares, n=6, 52.4 ± 3.6 fmoles/sample, and n=6, 51.8 ± 4.4 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the core; n=9, 44.2 ± 3.7 fmoles/sample, and n=6, 29.1 ± 3.1 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the shell) and in animals pretreated with RIM 3 mg/kg and cocaine (▵, unfilled triangles, n=6, 59.1 ± 5.7 fmoles/sample, and n=6, 52.1 ± 9.1 fmoles/sample, for cocaine 10 and 20 mg/kg, respectively in the core) or pretreated with RIM 3 mg/kg and saline (∎filled squares, n=4, 35.0 ± 7.7 fmoles/sample, for cocaine 20 mg/kg in the core) 24 hr before microdialysis tests. [Three-Way ANOVA (RIM pretreatment X cocaine treatment X time) showed in the core significant main effects of cocaine dose F(1,42)= 15.296, p<0.001, RIM pretreatment F (3, 42) = 3.168, p<0.05, and time F (6,252)= 91.066, p<0.001; also, there were significant interactions of cocaine dose × time F(18,252) = 19.735, p<0.001, RIM pretreatment × time F(18,252)= 2.297, p<0.05; non-significant interactions of RIM pretreatment × cocaine dose F (3.42)=0.518, NS; and pretreatment × cocaine dose × time interaction F= (18,252)= 0.486, NS. Three-Way ANOVA in the shell showed significant main effects of cocaine dose F(1,36)= 24.057, p<0.001, and time F (12,432)= 101.088, p<0.001, and a non-significant main effect of RIM pretreatment F (2, 36) = 0.139; also, there were significant interactions of cocaine dose × time F(12,432) = 19.735, p<0.001, non-significant interactions of pretreatment × cocaine dose F (2,36)=0.872; pretreatment × time F(24,432)= 1.007; and pretreatment × cocaine dose × time interaction F= (24,432)= 0.594]. Results are means with vertical bars representing S.E.M. of the amount of DA in 10 minutes dialysate samples, expressed as percentage of basal values.