Chronic Administration of Carvone-Rich Mentha spicata L. Essential Oil Attenuates Cognitive Dysfunction and Oxidative Stress in Zebrafish

Cognitive impairment and anxiety-like behavior associated with cholinergic dysfunction and oxidative stress remain important experimental targets for neuropharmacological screening. Mentha spicata essential oil (MEO, 150 or 300 µL/L) was administered daily by immersion from experimental day 1 through day 22; the first behavioral assessment occurred after 7 days of pre-exposure. Scopolamine hydrobromide trihydrate (SCO, 100 µM) was administered for 30 min before each behavioral assessment and again before euthanasia, whereas galantamine (GAL, 1 mg/L) was administered 30 min before each SCO challenge. Behavior was evaluated using the novel tank diving test (NTT), novel approach test (NAT), Y-maze, and novel object recognition test (NOR). Brain acetylcholinesterase (AChE) activity, antioxidant defenses, and oxidative damage were assessed. GC-MS identified a carvone-rich profile dominated by carvone (67.8%), limonene (10.6%), and 1,8-cineole (4.2%). MEO attenuated several SCO-associated behavioral and biochemical changes. The 150 µL/L concentration showed the most consistent memory-related improvement, whereas 300 µL/L also reduced selected oxidative markers but was associated with reduced exploratory activity in some tasks. Treatment-adjusted behavior–biomarker analyses were considered exploratory; only the inverse association between malondialdehyde (MDA) and the NTT top/bottom ratio remained significant after false-discovery-rate correction. In silico descriptors were treated as hypothesis-generating and do not demonstrate zebrafish brain exposure. These findings support further investigation of carvone-rich MEO within a rescue/protection framework, with confirmation in independently replicated exposure tanks and inclusion of MEO-only controls.