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Fig. 3 | Molecular Brain

Fig. 3

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. 3

Ketamine restores SC-CA1 sLTP in WKY rats at 3.5 h but not 30 min after injection, with residual effects at 24 h. a, b WKY saturated LTP at 30 min post-injection by (a) drug treatment and (b) time bin (SAL: n = 12, KET: n = 5). Ketamine administration had no significant acute effects on WKY basal synaptic transmission. Although sLTP induction only reached significance in saline (***p < 0.0001) but not ketamine (p = 0.14, n.s.) treated rats, there were no significant differences between the two groups at any time point, and no significant sLTP was observed at 90 min as before, regardless of the treatment group (statistically significant decay in SAL rats only, ‡ ‡ ‡p = 0.0008). c, d WKY sLTP at 3.5 h post-injection by (c) drug treatment and (d) time bin (SAL: n = 19, KET: n = 18). Initially, significant sLTP was observed in both groups (***p < 0.0001); however, while potentiation again completely decayed in saline-treated WKYs (‡ ‡ ‡p < 0.0001), robust sLTP was still present at 90 min post-HFS in the ketamine group following only partial decay (***p < 0.0001; ‡ ‡p = 0.003; vs. SAL # # #p = 0.0003). e, f WKY sLTP at 24 h post-injection by (e) drug treatment and (f) time bin (SAL: n = 12, KET: n = 10). Significant sLTP was induced in both saline (***p = 0.0004) and ketamine (***p = 0.0009) treated WKYs; however, while the potentiation again completely decayed over the 90 min in the saline group (‡ ‡p = 0.0024), only partial decay was observed following ketamine (p = 0.17, n.s.), so that some sLTP was still present 90 min post-HFS (p = 0.097, n.s.). (G) WKY I/O curves at 24 h (SAL: n = 12, KET: n = 10, same rats as in (e, f)). fEPSP slope across all current intensities was consistently higher 24 h following ketamine compared to saline treatment, with the stimulation magnitude evoking ~ 50% of the maximal response effectively shifted leftward (from 100 μA to 60 μA) in ketamine-treated rats. h WIS sLTP at 3.5 h post-injection by drug treatment (SAL: n = 6, KET: n = 3). Ketamine had no significant acute effects on WIS basal synaptic transmission. Significant sLTP was observed in both saline p = 0.0003) and ketamine p < 0.0001) treated WIS rats, and independent of the treatment group, robust sLTP was still present 90 min later (SAL: p = 0.028 and KET p = 0.013). Single big arrow = drug injection, 4 small arrows = strong HSF protocol; * vs. [1] = potentiation effect, vs. [2] = decay effect, # vs. SAL = treatment effect; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001

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