Dorsal hippocampal CA۱ NMDA receptors mediate the interactive effects of quetiapine and lithium on memory retention in male rats

Objective(s): Lithium and quetiapine are administered simultaneously as a treatment for bipolar disorder. The concurrent use of these two drugs has been observed to affect the neurobiological mechanisms underlying learning and memory. To clarify the precise mechanisms involved, we evaluated the possible role of the dorsal hippocampal CA۱ NMDA receptors in the interactive effects of lithium and quetiapine in memory consolidation. Materials and Methods: The dorsal hippocampal CA۱ regions of adult male Wistar rats were bilaterally cannulated, and a single-trial step-through inhibitory avoidance apparatus was used to assess memory consolidation. Results: Post-training administration of certain doses of lithium (۲۰, ۳۰, and ۴۰ mg/kg, IP) diminished memory consolidation. Post-training administration of higher doses of quetiapine (۵, ۱۰, and ۲۰ mg/kg, IP) augmented memory consolidation. Post-training administration of certain doses of quetiapine (۲.۵, ۵, ۱۰, and ۲۰ mg/kg) dose-dependently restored lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (۱۰-۵ and ۱۰-۴ µg/rat, intra-CA۱) plus an ineffective dose of quetiapine (۲.۵ mg/kg) restored the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the noncompetitive NMDA receptor antagonist, MK-۸۰۱ (۰.۰۶۲۵ and ۰.۰۱۲۵ μg/rat, intra-CA۱), diminished the quetiapine-induced (۱۰ mg/kg) memory improvement in lithium-induced memory impairment.Conclusion: These findings suggest a functional interaction between lithium and quetiapine through hippocampal CA۱ NMDA receptor mechanisms in memory consolidation.

کلیدواژه ها:

Dorsal hippocampus ، Lithium ، MK-۸۰۱ ، N-methyl-D-aspartic acid ، Quetiapine