Figure 4.
High dose of cocaine induces incubation of cocaine craving and inserts GluA2-lacking AMPARs in D2R-MSN. (a) Schematic of the experiment. (b) Inactive, active lever presses and relative presses are represented for each mouse during cue-induced cocaine-seeking sessions (1 h) at withdrawal days 1 and 30 (WD1 and WD30) (bottom) from cocaine SA (10 daily sessions of 2 h with 0.75 mg/kg/infusion of cocaine) (N=6). (c) Number of infusions (top) and lever presses (active and inactive) during the 10 days of acquisition are represented for mice submitted to long-access sessions (6 h) with either 0.75 (top) or 1.5 mg/kg/infusion (bottom) of cocaine (N=13–29 mice). Dunnett's post-test for infusions: *P<0.01 when compared with first session; Bonferroni post-test: *P<0.01 for active vs inactive. (d) Individual number of inactive, active lever presses and relative active lever presses during the cue-induced cocaine seeking at WD1 and 30. Incubation of cocaine craving was present for the high concentration of cocaine per infusion, but not for the regular concentration (N=10–11). *P<0.05 or **P<0.01 for WD 30 vs WD 1. (e) Example traces of AMPAR-EPSCs recorded at −70, 0, and +40 mV. (f) I–V relationship for AMPAR-EPSCs in D1 and D2-MSN from regular or high dose of cocaine SA mice (N=9–17 cells from 3 and 6 mice, respectively). Bonferroni post-test **P<0.01 or ***P<0.001, for cocaine vs saline and °°°P<0.001 for D1 vs D2. Dashed lines represented values obtained from saline SA in the experiment of Figure 3. (g) Quantification of the RI for AMPAR-EPSCs in D1 and D2-MSN from regular or high dose of cocaine SA mice (N=9–17 cells from 3 and 6 mice, respectively). Bonferroni post-test **P<0.01 or ***P<0.001, for cocaine vs saline and °°°P<0.001 for D1 vs D2. Dashed lines represented values obtained from saline SA in the experiment of Figure 3. Scale bars, 20 ms, 20 pA. Data are expressed as mean±SEM. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; EPSC, excitatory postsynaptic current; MSN, medium-sized spiny neuron; SA, self-administration.