International journal of molecular sciencesOct 27, 2026

Similar Fast Antidepressant Effects of Two Low Ketamine Doses Linked to Different Molecular Changes in Brain Areas After Teen Stress

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Updated Oct 28, 2026

Abstract

A single injection of ketamine at 6 or 10 mg/kg significantly reduced immobility in the tail suspension test 24 hours after treatment.

Both subanesthetic doses of ketamine produced similar acute antidepressant-like effects in stressed mice.
The reduction in immobility was not sustained one week after treatment.
Molecular analyses showed dose- and region-dependent regulation of signaling markers in the prefrontal cortex, hippocampus, and striatum.
The higher ketamine dose resulted in more extensive molecular changes without a corresponding increase in behavioral improvement.
The findings suggest that the effects of ketamine on behavior may depend on specific brain regions rather than the overall activation level of molecular pathways.

Simplified

Ketamine produces rapid antidepressant-like effects across a range of subanesthetic doses, yet how dose shapes behavioral efficacy and region-specific molecular signaling following adolescent chronic unpredictable stress (CUS) is not well understood. Here, we examined the behavioral and molecular consequences of two subanesthetic ketamine doses in adult mice with depression-like behavior induced by CUS. Male C57BL/6J mice were exposed to CUS during adolescence and developed depression-like behavior in adulthood. Adult mice received a single injection of vehicle or ketamine at 6 or 10 mg/kg, while non-stressed controls received vehicle. Both ketamine doses reduced immobility in the tail suspension test 24 h after treatment, indicating comparable acute antidepressant-like effects; however, this effect was not sustained one week later. Molecular analyses of the prefrontal cortex, hippocampus, and striatum were performed 24 h after behavioral testing, corresponding to 48 h after ketamine administration, to define region-specific ERK, mTOR, JNK, and BDNF signaling profiles. These analyses revealed dose- and region-dependent regulation of all four markers. The higher ketamine dose produced more extensive molecular changes without producing a greater reduction in tail-suspension test (TST) immobility, suggesting that the behavioral relevance of ketamine-induced signaling depends on regional context rather than the overall magnitude of pathway activation.

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Similar Fast Antidepressant Effects of Two Low Ketamine Doses Linked to Different Molecular Changes in Brain Areas After Teen Stress

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