Ketamine via Oral Gavage

In this paper we investigated the behavioral and neural effects of orally administered ketamine in adult rats. Animals received either saline or ketamine at 15, 30, or 45 mg/kg and were tested in the forced swim test, open field, fear conditioning, and elevated plus maze. We also examined changes in brain activity and NMDA receptor subunits using protein assays and immunohistochemistry. The highest dose (45 mg/kg) reduced immobility in the forced swim test, briefly impaired fear memory, and lowered stress-related vocalizations. Ketamine also changed NMDA receptor expression in depression-related brain regions such as the thalamus, amygdala, and habenula. High doses further reduced stress-induced neural activation in the medial habenula. Overall, our results show that oral ketamine at 45 mg/kg produces antidepressant-like effects by altering activity in key mood-related circuits.

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