FIGURE 1.

THC + CBD self-administration and cue-induced reinstatement induces a loss and restoration of LTD, respectively. A, The three treatment groups used throughout the study: vehicle-extinguished (Ctrl), THC + CBD-extinguished (Ext), THC + CBD-reinstated (Rst). B, SA of THC + CBD followed by extinction training. Note that the discrimination between active and inactive levers during SA is no longer apparent by day 4 of extinction (except for day 8 + 9) *P < .05, comparing active and inactive lever, N = 27. C, Active and inactive lever pressing during 30 minutes of cued-reinstatement. Dashed line indicates reinstatement criterion of greater than10 active lever presses. *P < .05, comparing Rst and non-Rst; ^#P < .05, comparing active and inactive lever presses. D, Time-course of synaptic response before and after LTD induction (arrows). Inset above: representative average pre- and post-traces for the three treatment groups; scale 200 pA and 20 ms. NAcore MSNs showed robust LTD in Ctrl (N = 7 cells/6 rats). Extinction of THC + CBD-induced metaplasticity (14 cells/8 rats) that was partly rectified by 30 minutes of cue-induced reinstatement (18 cells/14 rats). *P < .05, 2-way ANOVA, main effect of time and treatment groups. E, Bar graph summarizing the average response 15 to 25 minutes after LTD induction. *P < .05, comparing baseline response to 15 to 25 postinduction. F, Time course of synaptic response before and after LTD induction for animals grouped into nonreinstaters (non-RST; N = 9 cells/7 animals) and reinstaters (RST; N = 9 cells/7 animals) according to criterion in Figure 1C. *P < .05, 2-way ANOVA, main effect of time and treatment groups. G, Bar graph illustrating significant LTD expression in Rst but not non-RST. *P < .05, comparing baseline response to response 15 to 25 postinduction