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. 2023 Feb 8;43(6):1038–1050. doi: 10.1523/JNEUROSCI.1316-22.2022

Figure 3.

Figure 3.

Blocking NMDAR activity prevents the antidepressant-relevant behavioral effects of distinct rapid-acting antidepressant compounds. A, B, Mice received an injection of vehicle or the NMDAR channel blocker MK-801 and 10 min later were given an additional injection of vehicle or ketamine's metabolite (2R,6R)-hydroxynorketamine (HNK; 10 mg/kg) and tested in the forced swim test 24 h later. While (A) the dose of 0.1 mg/kg MK-801 completely prevented the antidepressant-like behavioral actions of (2R,6R)-HNK, (B) 0.03 mg/kg MK-801 did not prevent (2R,6R)-HNK's actions to decrease immobility time in the forced-swim test. MK-801 pretreatment (0.1 mg/kg) prevented the antidepressant-relevant behavioral actions of (C) the negative allosteric modulator of GABAA receptors containing α5 subunits (GABA-NAM) MRK-016 in the forced-swim test. MK-801 pretreatment (0.1 mg/kg) prevented the antidepressant-like effects of (D) (2R,6R)-HNK, (E) MRK-016, and (F) the mGlu2/3 receptor antagonist LY341495 in the learned helplessness paradigm 24 h following drug administration. Data are the mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001 as indicated by Holm–Šídák post hoc comparisons. See Table 1 for complete details on the statistical analyses and precise group sizes. KET, racemic ketamine; SAL, saline.