Briana K Chen, Victor M Luna, Michelle Jin, Abhishek Shah, Margaret E Shannon, Michaela Pauers, Brenna L Williams, Vananh Pham, Holly C Hunsberger, Alain M Gardier, Indira Mendez-David, Denis J David, Christine A Denny
BACKGROUND: Serotonin (5-HT) receptors and N -methyl-D-aspartate receptors (NMDARs) have both been implicated in the pathophysiology of depression and anxiety disorders. Here, we evaluated whether targeting both receptors through combined dosing of ( R , S )-ketamine, an NMDAR antagonist, and prucalopride, a serotonin type IV receptor (5-HT 4 R) agonist, would have additive effects, resulting in reductions in stress-induced fear, behavioral despair, and hyponeophagia. METHODS: A single injection of saline (Sal), ( R , S )-ketamine (K), prucalopride (P), or a combined dose of ( R , S )-ketamine and prucalopride (K+P) was administered before or after contextual fear conditioning (CFC) stress in both sexes...
September 27, 2023: bioRxiv