Chronic, combinatorial targeting of NMDARs and 5-HT4Rs exerts extended behavioral effects against stress-induced perseverative behavior and hyponeophagia.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology April 22, 2025 Briana K Chen, Alicia Whye, Louise C Matthews et al. 2 citations
A combination of two FDA-approved drugs—(R,S)-ketamine, an anesthetic and NMDAR antagonist, and prucalopride, a 5-HT4 receptor agonist used for constipation—reduced stress-induced behavioral changes in male and female rodents after various stressors (fear conditioning, learned helplessness, stress-enhanced fear learning, and chronic corticosterone exposure). The combined treatment was more effective than either drug alone, and intranasal delivery also worked. Chronic administration of the combination broadly alleviated stress-related behaviors, suggesting potential for treating stress-induced psychiatric disorders in humans.