Cola nut is a caffeine-containing nut of evergreen trees of the genus Cola, primarily of the species Cola acuminata and Cola nitida. It is one of the most common chewable nut in Nigeria. It is a central nervous system stimulant used in folk medicine as an aphrodisiac, an appetite suppressant, to treat migraine headache and indigestion. The aim of the present study was to investigate the possible effects of Cola nitida extracts on the cerebral cortex, hippocampus and some biochemical parameters. Forty (40) adult Long Evans rats of both sexes, with average weight of 210-230grams were randomly divided into four groups: A (control) = four rats (administered normal feed and distilled water);B= caffeine fraction group containing three sub groups of four rats each, B1, B2 and B3 were administered with di-chloromethane caffeine fractionof 19.2, 38.4 and 57.6mg/kg body weight, respectively; C= aqueous extract group containing three sub groups of four rats each, C1, C2 and C3 and were administered cola nut aqueous extract orally at the concentration of 300, 600 and 900 mg/kg body weight respectively; D= cola nut supplement group containing three sub groups of four rats each, D1, D2 and D3 were administered 10%, 20% and 30% w/w cola nut supplemented feed, respectively. The administration lasted for a period of 21 days (3 weeks). Behavioural test for spatial learning and memory was carried out using Morris water maze and anxiety-like behaviours using Elevated Plus Maze. Blood was collected via cardiac puncture for determination of haematological indices, Brain tissues used for determination of oxidative stress parameters were homogenised in cold saline thoseused for histological studies were fixed in Bouin?s fluid processed and stained using Haematoxylin and Eosin (H and E) and toluidine blue stains. The Morris water maze test showed a non-significant decrease (P?0.05) in time to find the platform in all the treatment groups. A non- significant increase (P?0.05) in the meantime spent in the open arm, number of entriesinto the open arm, rearing and number of head dips in the elevated plus maze test when compared with the control was observed. The result of the oxidative stress markers showedstatistical significant decrease insuperoxide dismutase (SOD) of the aqueous and caffeine fraction groups when compared with the control.No significant difference was observed with the other markers. The results of the haematological indices revealed a statistical significant increase(p?0.05) anddecrease (P?0.05) in lymphocytes and neutrophils counts respectively in the caffeine and aqueous extract groups. The histology results revealed neurodegenerative changes in the cerebral cortex and hippocampus of the treated groups, which range from neuronal degeneration, pyknosis and clumping of pyramidal cells in the hippocampus. It was concluded that ingestion of cola nut and its constituent by Long Evans rats caused no significant effect on learning and memory, decreased anxiety-like behaviours, anti-inflammatory effect by increasing lymphocytes and decreasing neutrophils level, non-antioxidant effect by significantly decreasing the level of superoxide dismutase (SOD) and neurodegenerative changes.