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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: Addict Biol. 2016 Nov 11;23(1):80–89. doi: 10.1111/adb.12475

Figure 1. Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

Figure 1

A. Timeline: Rats were trained to self-administer cocaine for 6 h/day for a total of 10 days, and tested for cue-induced cocaine seeking on either WD1 or WD15. During this two week withdrawal period, rats were exposed to repeated restraint stress sessions or control conditions (7 sessions over a 9 day period, from WD6-WD14). B. Self-Administration Training: Data are presented as mean ± SEM number of cocaine infusions and active hole (AH) and inactive hole (IH) nose-pokes averaged over the 10 days of self-administration training. C. Seeking Tests: Nose-pokes in the previously active hole (left) and the inactive hole (right) during the seeking tests on WD1 and WD15. During the seeking tests, active hole nose-pokes led to contingent presentation of a 20-sec light cue previously paired with each cocaine injection. The number of responses made under these conditions is the operational measure of cue-induced cocaine craving. Nose-pokes in the inactive hole had no consequences. Data are expressed as mean ± SEM number of active and inactive hole nose-pokes. While controls demonstrated a time-dependent increase in cue-induced cocaine seeking behavior on WD15 compared to WD1 (i.e., incubation), animals that were exposed to repeated restraint stress showed significantly greater seeking compared to controls on WD15 (*p<0.05). AVG, average; SA, self-administration; WD, withdrawal day.