Fig. 2
Intra-dHPC Lei-Dab7 facilitates the formation of morphine-context memory with subthreshold (2 days) conditioning. (A) Schematic of the experimental timeline for the subthreshold 2-day conditioning MorCPP protocol. Intra-dHPC saline or Lei-Dab 7 infusions were administered before afternoon conditioning sessions to evaluate SK2 channel’s role in memory formation. (B) Two days of morphine conditioning were insufficient to induce a significant preference for the morphine-paired compartment. However, mice that received Lei-Dab7 (10 ng/µl) prior to conditioning sessions showed a strong preference for the morphine-paired compartment, suggesting that blocking SK2 channels facilitates the formation of morphine-context memory, as fewer conditioning sessions were required to induce significant preference (n = 7–8; Three-way RM ANOVA, Pre vs. Post x Sal vs. Mor: F1,26 = 9.274, p = 0.0053 with Sidak’s multiple comparisons). (C) Similarly, only morphine-conditioned mice that received intra-dHPC Lei-Dab7 showed a significant increase in CPP score compared to its saline-conditioned counterpart (Two-way RM ANOVA, Sal vs. Mor: F1,26 = 15.62, p = 00005 with Sidak’s multiple comparisons; $$Mor-10ng/µl vs. Sal-10ng/µl) and from 0 (One-sample t-test, Mor-LeiDab: t7 = 4.345, **p = 0.0034). (D) Intra-dHPC Lei-Dab 7 had no effect on locomotion during conditioning, as morphine-conditioned mice exhibited similar distances traveled on conditioning day 1 regardless of the intra-dHPC treatment (Three-way RM ANOVA, Time x Sal vs. Mor: F8,208 = 121.5, p < 0.0001). Data are expressed as mean ± S.E.M. or as mean with before-after pairing.
