Behavioral pharmacologyThe effects of subchronic d-serine on left-right discrimination learning, social interaction, and exploratory activity in APPswe/PS1 mice

Glutamatergic neurotransmission is crucially involved in memory and cognition and severely affected patients with Alzheimer's disease. Modulation of NMDA receptors with agonists may reverse their late-stage symptoms. The effects of subchronic treatment of the NMDA receptor agonist, d-serine, were evaluated in APPswe/PS1 mutant mice harboring Aβ plaques in brain, regarding spatial discrimination learning, open-field activity, and social interaction in a three-chambered apparatus. d-serine (50 mg/kg, i.p.) was superior to placebo in mutant mice during the reversal phase of left-right discrimination learning without affecting acquisition. The drug caused weaker effects in counteracting open-field hyperactivity and low social interaction with an unfamiliar stimulus mouse. These results indicate a favorable action of an NMDA receptor agonist on reversal learning in transgenic mice with amyloid pathology.