Dorsal hippocampal CA1 NMDA receptors mediate the interactive effects of quetiapine and lithium on memory retention in male rats

Treatment of bipolar disorder with simultaneous lithium and quetiapine administrations is a prime medical topic due to the ambiguities surrounding the neurobiological mechanisms underlying learning and memory. To clarify the precise mechanisms involved, we evaluated the possible role of the dorsal hippocampal CA1 NMDA receptors in the interactive effects of lithium and quetiapine in memory consolidation. For this purpose, the dorsal hippocampal CA1 regions of adult male Wistar rats were bilaterally cannulated, and a single-trial step-through inhibitory avoidance apparatus was used to assess memory consolidation. Post-training administration of certain doses of lithium (20, 30, and 40 mg/kg, i.p.) diminished memory consolidation. Post-training administration of higher doses of quetiapine (5, 10, and 20 mg/kg, i.p.) augmented memory consolidation. Post-training administration of certain doses of quetiapine (2.5, 5, 10, and 20 mg/kg) dose-dependently improved lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (10-5 and 10-4 µg/rat, intra-CA1) plus an ineffective dose of quetiapine (2.5 mg/kg) improved the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the noncompetitive the NMDA receptor antagonist, MK-801 (0.0625 and 0.0125 μg/rat, intra-CA1), diminished the quetiapine-induced (10 mg/kg) memory improvement in lithium-induced memory impairment. These findings suggest a functional interaction between lithium and quetiapine through hippocampal CA1 NMDA receptor mechanisms in memory consolidation.