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. 2015 Sep 30;35(39):13300–13310. doi: 10.1523/JNEUROSCI.1065-15.2015

Figure 4.

Figure 4.

Dark-phase SR reduces incubation of cocaine craving and prevents synaptic accumulation of CP-AMPARs in the NAc. A, Timeline of cocaine self-administration training, withdrawal, and repeated dark-phase SR during different periods after withdrawal (on withdrawal days 36–42, 29–42, 22–42, 1–42). Cocaine-exposed rats without SR were used as controls. The same rats were tested on withdrawal days 1 and 45. B, Left, Cue-induced cocaine seeking (measured by the number of nose pokes in the active hole during the daily 2 h training session or the 0.5 h test session) in the control group was enhanced on withdrawal day 45 compared with day 1, suggesting incubation of cocaine craving. Following different periods of dark-phase SR, cue-induced cocaine seeking was reduced in a “dose”-dependent manner on withdrawal day 45, with longer durations of SR exhibiting larger anti-incubation effects. *p < 0.05 (different from control group on withdrawal day 45). Color coding is the same as in A. Right, Cue-induced nose pokes in the inactive hole (not associated with cocaine delivery) remained low as in controls. C, Timeline of cocaine self-administration training, withdrawal, repeated dark-phase SR (on withdrawal days 22–42), and sucrose self-administration training. Cocaine-exposed rats without SR were used as controls. D, E, Sucrose self-administration learning following long-term cocaine withdrawal was not altered in the SR group compared with the control, as measured by the number of lever presses on the active lever (D) or percentage active/total lever presses (E), suggesting no effect of SR on natural reward seeking. F, Timeline of cocaine self-administration training, withdrawal, and repeated dark-phase SR (on withdrawal days 22–42). G, Evoked EPSCs from an example NAc MSN before and during perfusion of CP-AMPAR-selective antagonist Naspm (100 μm) in an NAc slice from a rat on withdrawal day 45. H, Evoked EPSCs from an example NAc MSN before and during perfusion of Naspm from a rat that received dark-phase SR between withdrawal days 22 and 42. I, Summarized results showing that the evoked EPSCs in NAc MSNs were less sensitive to Naspm inhibition in the dark-phase SR group. **p < 0.01 (different from cocaine-exposed rats without SR). Numbers in parenthesis represent number of cells/number of rats. Error bars indicate SEM.