Background: Nicotine is the addictive component of tobacco smoking. It has been reported to have a negative neuromodulatory role in the CNS. Moringa oleifera is a medicinal plant with reported antioxidant, anticonvulsant, anti-inflammatory and neuroprotective
properties. Aim and Objectives: This study was purposed to investigate the neuronal adaptation potentials of Moringa Oleifera (MO) on nicotine induced behavioural decline and perturbed bioenergetics. Material and Methods: Twenty-four adult male Wistar rats were used. The treatment regimen was as follows; control group received distilled water, MO group received 200 mg/kg of MO, Nicotine Group received 1.38 mg/kg body weight of nicotine, and Nicotine + MO group received combined treatment of
200 mg/kg body weight of MO after 1.38 mg/kg body weight of nicotine for 28 days. The animals were subjected to Morris water maze for spatial memory, Y maze for working memory and elevated-plus maze tests for anxiety levels after which they were sacrificed for spectrophotometric analysis of global protein expression, neural bioenergetics (lactate dehydrogenase
and glucose-6-phosphate dehydrogenase), and Acetylcholinesterase (AChE) levels. Results: Nicotine infusion caused a reduction in the escape latency period, increased the percentage incorrect alternation, and elevated the anxiety levels of rats. These observations were indicative of decreased synaptic
activity in the brain. Together with, nicotine induced chromatolytic changes in cells of the frontal cortex and hippocampus. Co-administration with MO prevented nicotine-associated memory decline, perturbed glucose bioenergetics, induced chromatolysis and histomorphological distortion in the frontal cortex and
hippocampus. Conclusion: Our data demonstrate that MO administration enhances experience-dependent neuroplasticity and cognitive behaviour function in laboratory animals, modulates energy metabolism and reduced oxidant stress possibly through enhanced production of key antioxidant enzymes against the
damaging effects of nicotine. It provided evidence that MO can be further developed as a means to protect the brain from oxidative stress-induced injury
