Effects of subanesthetic intravenous ketamine infusion on corticosterone and brain-derived neurotrophic factor in the plasma of male Sprague-Dawley rats

Posttrauma anesthetic agents influence neuroendocrine responses that may affect fear memory. The effects of a subanesthetic intravenous (IV) ketamine infusion on mediators of stress and memory in rodents are unknown. Therefore, we used a clinically relevant method to administer a 2-hour subanesthetic IV ketamine infusion following a rodent fear-conditioning paradigm (paired tone plus foot shock) to evaluate the effects on corticosterone and brain-derived neurotrophic factor in the plasma of male Sprague-Dawley rats. We found that subanesthetic ketamine infusions (5 and 20 mg/kg/h) dose-dependently increased plasma corticosterone levels. Ketamine at 20 mg/kg/h significantly reduced plasma brain-derived neurotrophic factor measured 2 hours after the conclusion of the ketamine infusion. These results demonstrate that a subanesthetic IV ketamine infusion maintained a heightened neuroendocrine stress response after fear conditioning and reduced levels of a neurotrophin associated with memory, which may influence fear memory processing. The behavioral outcomes of these effects are unknown and warrant future investigation.