Neurotransmitter Mechanisms of Ketamine and Ketamine–Magnesium Sulfate-Induced Hypothermia: Evidence for Serotonergic and Adrenergic Involvement Without GABAA Contributions
Brain Sciences February 4, 2026 Katarina Savić Vujović, Sonja Vučković, Lara Samardžić et al.
Ketamine and a ketamine-magnesium sulfate combination lower body temperature in rats through serotonergic and adrenergic mechanisms, but not through GABAA receptors. Giving yohimbine, an α2-adrenergic blocker, deepened ketamine-induced hypothermia at doses of 0.5 and 1 mg/kg, while only the highest dose (3 mg/kg) enhanced the combination's effect. Methysergide, a serotonin blocker, had opposite effects depending on dose: 1 mg/kg worsened ketamine hypothermia, whereas 0.5 mg/kg reduced the combination's cooling effect. Bicuculline, a GABAA antagonist, did not change hypothermia from either treatment. These findings clarify neurotransmitter pathways involved in NMDA antagonist-related thermoregulation.