<p>The Na⁺,K⁺-ATPase plays a fundamental role in memory formation by regulating neuronal excitability and NMDA receptor-dependent synaptic plasticity. While this enzyme’s dysfunction is broadly linked to cognitive disorders, its specific contribution to fear memory consolidation, particularly within the key brain structure of the basolateral amygdala (BLA), remains undefined. We investigate whether Na⁺,K⁺-ATPase inhibition disrupts contextual fear conditioning (CFC) memory consolidation and examine downstream molecular, oxidative, and inflammatory responses in interconnected brain regions. Fifty-day-old male Wistar rats received bilateral cerebral infusions of the Na⁺,K⁺-ATPase inhibitor ouabain (1&#xa0;μm) or vehicle immediately after CFC training. Memory retention was assessed 24&#xa0;h later. Additional cohorts were euthanized 6–24&#xa0;h after infusion for biochemical analysis of Na⁺,K⁺-ATPase activity, expression of Na⁺,K⁺-ATPase isoforms (α1, α2, α3, β1), oxidative stress markers, and pro-inflammatory cytokines in the amygdala, hippocampus, and prefrontal cortex. Post-training Na⁺,K⁺-ATPase inhibition in the BLA selectively impaired fear memory consolidation. Ouabain induced changes in Na⁺,K⁺-ATPase activity in the hippocampus and prefrontal cortex, and induces time-dependent upregulation of α1 and β1 isoforms. Six hours after infusion, ouabain triggered oxidative imbalance – characterized by reduced CAT activity. Pro-inflammatory cytokine expression was markedly elevated in the hippocampus and prefrontal cortex, while D-serine co-administration failed to rescue memory deficits. These findings establish a previously unrecognized role for Na⁺,K⁺-ATPase signaling in the BLA in coordinating the neurobiological processes essential for fear memory consolidation, indicating that its precise regulation is required for adaptive fear memory formation.</p>