The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic
xenobiotics, including
organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two
organophosphates,
chlorpyrifos (CPF) and
dichlorvos (
DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150⁻170 g) were randomly divided into four groups, orally exposed to
normal saline (NS),
DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and
DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze
nitric oxide (NO) metabolites, total
reactive oxygen species (ROS), and
acetylcholinesterase (AChE) activity, and the other three were processed for histology (
cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in
body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and
DDVP. Insults from
DDVP exposure appeared more severe owing to the observed greater losses in the
body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-
cognitive dysfunction and increased anxiety-like behaviors that follow
organophosphate poisoning.