Gallic acid attenuates PTSD-like behavioral and hippocampal neuroplasticity deficits induced by single prolonged stress in male rats.

Post-traumatic stress disorder (PTSD) is associated with persistent cognitive and emotional disturbances linked to hippocampal dysfunction, oxidative stress, and impaired neuroplasticity. Gallic acid, a naturally occurring polyphenol, possesses antioxidant and neuroprotective properties, but its effects in trauma-related disorders remain incompletely understood. Male Wistar rats were subjected to single prolonged stress (SPS) to induce PTSD-like phenotypes and, beginning 24 h after SPS, received gallic acid (10 or 100 mg/kg) or saline for 14 days. Anxiety-like behavior, fear extinction, and spatial learning and memory were assessed using the elevated plus maze, contextual fear conditioning with extinction, and Morris water maze, respectively. Hippocampal oxidative stress markers (MDA, SOD, and TAC), BDNF protein expression, and CA3 dendritic morphology were evaluated. SPS exposure induced anxiety-like behavior, impaired fear extinction, and deficits in spatial learning and memory, accompanied by increased lipid peroxidation, reduced antioxidant capacity, decreased hippocampal BDNF expression, and CA3 dendritic atrophy. Early post-stress gallic acid administration attenuated these behavioral alterations and was accompanied by improvements in hippocampal oxidative status, BDNF expression, and CA3 dendritic morphology, without detectable effects on locomotor activity or relative adrenal gland weight. Collectively, these findings indicate that early post-stress gallic acid administration attenuates SPS-associated behavioral and hippocampal abnormalities and that these effects are associated with antioxidant and neuroplasticity-related changes rather than establishing a causal mechanism. Further studies using delayed treatment paradigms and pathway-specific approaches are needed to determine the efficacy of gallic acid after establishment of the PTSD-like phenotype and to clarify the mechanisms underlying its effects.