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Fig. 4 | Molecular Brain

Fig. 4

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. 4

Ketamine restores NOLRT long-term spatial memory in WKY rats, without affecting performance in WIS controls. a In the NOLRT, following 3 days of habituation (H1–3), rats received 2 training sessions (T1 and T2, 10 min each), with two identical objects placed in two opposing arena corners. During the testing session (T3, 1 h or 24 h later for short or long -term memory), one object stayed at the familiar location (FL), while the other was moved to a new location (NL), where an NL preference (NL/NL + FL) of 60% or more indicates strong hippocampal-dependent spatial memory. In experiments involving drug treatment (purple arrows), saline, ketamine or (2R,6R)-HNK were injected 3.5 h before T2, i.e. 27.5 h before the 24 h testing session (T3). b Total NOLRT T3 exploration time (NL + FL) at 1 h or 24 h (n = 8–12/group) was comparable between the two strains. c % NL preference for the NOLRT test session for drug-free (1 h or 24 h) and drug-treated (saline or ketamine) WKY and WIS rats. Under drug-free conditions (1 h/24 h drug-naïve: n = 8–12/strain, same rats as in (b)), short-term memory (at 1 h) was equivalent between strains; however, long-term spatial memory (at 24 h) was significantly impaired in WKY compared to WIS rats (#p = 0.027; WKY 1 h vs. 24 h ‡ ‡p = 0.0037). In drug-treated rats (24 h SAL/KET WKY: n = 25/group and WIS: n = 10/group), while NOLRT location recognition memory at 24 h remained impaired in saline treated WKY compared to WIS rats (#p = 0.05), ketamine administration significantly facilitated long-term spatial memory compared to saline-treated WKYs (***p = 0.0008), effectively restoring performance to control WIS levels (~ 60% at 24 h). Ketamine had no effect on NOLRT performance in WIS controls. # vs. WIS = strain effect, drug-naïve 24 h vs. 1 h = time delay effect, * vs. SAL = treatment effect; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001

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