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. 2021 Jun 3;118(23):e2023750118. doi: 10.1073/pnas.2023750118

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Fig. 6. — Procognitive action of D₃R antagonist S33084 relies on d-serine modulation of NMDARs. (A) Administration of the D₃R antagonist S33084 (0.63 mg/kg, s. c.) reverses the impairment in NOR memory induced by a 4-h ITI in rats (n = 12). Systemic administration of the NMDAR antagonists, MK801 (n = 12) and CPP (n = 12), as well as the glycine/d-serine binding site blocker L701,324 (n = 12) all prevented the enhancement of NOR memory induced by S33084. (B) Administration of the D₃R antagonist S33084 (0.63 mg/kg, s. c.) reversed the impairment in NOR memory induced by a 2-h ITI in SR^+/+ mice (vehicle, n = 14; S33084, n = 18) but not in SR^−/− mice (vehicle: n = 9; S33084, n = 10). The procognitive effect of S33084 is rescued in SR^−/− mice by chronic supplementation of d-serine (SR^+/++saline, n = 7; SR^−/−+d-ser, n = 8) performed by s. c. administration with 300 mg/kg d-serine (or control saline) on day 1 and then 150 mg/kg d-serine (or control saline) daily for 20 d. **P < 0.01, ***P < 0.001 compared with control SR^+/+ mice treated with vehicle. ⁺⁺P < 0.01, ⁺⁺⁺P < 0.001 compared with SR^+/+ mice treated with S33084.