Fig. 2. Behavioral sensitization to cocaine is associated with transient D1R-NMDAR heteromerization and prolonged D2R-NMDAR heteromerization in the NAc.
(A) Experimental time frame [NAc core and NAc shell and measurements of locomotor activity before and during 5 days of saline or cocaine (15 mg/kg) injections]. Two-way analysis of variance (ANOVA): treatment effect, F1,24 = 67.79, ***P < 0.0001 saline versus cocaine on day 5, n = 13 mice per group. DM, dorso-medial striatum; DL, dorso-lateral striatum. (B) Detection and quantifications of D1R-NMDAR heteromerization in saline- and cocaine-treated groups. PLA signal is represented as fold increase normalized to the saline group. Two-sided Student’s t test: *P < 0.05, **P < 0.01, and ***P < 0.001 (saline versus cocaine); n = 28 to 84 fields of view per structure (NAc core, 4; NAc shell, 12; DM, 6; DL, 6; fields of view per mice) from seven mice per group. (C) Same as for (B) for D2R-NMDAR heteromerization. (D) Experimental time frame, measurements of locomotor activity, and quantifications of D1R-NMDAR and D2R-NMDAR heteromerization. PLA signal is represented as fold increase normalized to the saline group. One-way ANOVA: *P < 0.05, **P < 0.01, and ***P < 0.001 (saline-saline versus cocaine-saline/cocaine-cocaine); #P < 0.05 and ##P < 0.01 (cocaine-saline versus cocaine-cocaine); n = 28 to 84 fields of view per structure from seven mice per group. (E) Same as for (D) except that mice received either a vehicle solution (Veh) or the D1R antagonist SCH23390 (SCH) or the D2R antagonist eticlopride (Etic) before a cocaine challenge. One-way ANOVA: **P < 0.01 and ***P < 0.001 (vehicle-saline versus vehicle-cocaine); #P < 0.05 and ##P < 0.01 (vehicle-cocaine versus SCH-cocaine or cocaine versus Etic-cocaine); n.s., not significant; n = 28 to 84 fields of view per structure from seven mice per group. Scale bars, 10 μm (B and C). Error bars denote SEMs.