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Fig. 5 | Molecular Brain

Fig. 5

From: Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression

Fig. 5

(2R,6R)-HNK restores SC-CA1 sLTP and NOLRT long-term spatial memory without affecting FST immobility in WKY rats. a, b WKY sLTP at 3.5 h post-injection by (a) drug treatment and (b) time bin (SAL: n = 19, HNK: n = 8, +KET: n = 18 in (b) only). (2R,6R)-HNK had no significant acute effects on WKY basal synaptic transmission. Significant sLTP was initially present in all groups (***p < 0.0001); however, potentiation immediately post-HFS was significantly higher in HNK treated rats compared to saline # #p = 0.0015) but also ketamine (†p = 0.017). In addition, while significant decay was seen in all groups (p ≤ 0.003, not shown), robust sLTP was still present 90 min later in the HNK-treated group (***p < 0.0001, vs. SAL # # #p < 0.0001), which is now similar in magnitude to that following ketamine, with no sLTP in the saline group as expected. Single big arrow = drug injection, 4 small arrows = strong HSF protocol; * vs. [1] = potentiation effect, # vs. SAL and vs. KET = treatment effects; c WKY % NL preference for the NOLRT test session (1 h/24 h drug-naïve: n = 9–12/group; SAL: n = 25, KET: n = 25 and HNK: n = 15). The WKY NOLRT long-term memory deficit (drug-naïve 24 h vs. 1 h, ‡ ‡p = 0.0037) was significantly reversed by (2R,6R)-HNK (vs. SAL *p = 0.012), as previously reported with ketamine (**p = 0.0017). drug-naïve 24 h vs. 1 h = time delay effect, * vs. SAL = treatment effect; d Average day2 FST immobility for saline (n = 7/group) and (2R,6R)-HNK (n = 9/group) treated WKY rats at 30 min and 24 h post-injection, indicating no effects of HNK in the FST. e Average total distance travelled in the OFT for saline and (2R,6R)-HNK treated WKY rats (n = 6/group) at 30 min or 24 h post-injection, where HNK had no effects on WKY general locomotor activity. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001

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