Engidawork,Ephrem(Prof.)Argaw,Hilina Melese2024-04-232024-04-232023https://etd.aau.edu.et/handle/123456789/2793Numerous studies have looked into the neurocognitive impact of cannabinoid ligands. The effect of Catha edulis (Vahl) Forssk. ex Endl. (Khat) on learning and memory is also researched by few scholars, although the findings were inconsistent. Moreover, the interaction of cannabis with other drugs of abuse is well studied. Indeed, recently, it was reported that the neurobehavioral effects of khat, such as motor tasks, working memory and anxiety-like behaviors are modulated by the endocannabinoid system. However, it is not known whether such modulation is apparent in spatial learning and memory. To this effect, mice 6–8 weeks old (6 per group) and a single dose of either crude khat extract orally (300mg/kg) alone or the cannabinoids intraperitonially (WIN-55,212-2 (1 mg/kg), JWH133 (5 mg/kg), cannabidiol (5 mg/kg), AM251 (1 mg/kg) and AM630 (1 mg/kg)) alone and in combination with crude khat were administerd according to their respective groups. Controls were administered with 0.5 ml of 2% Tween 80 in water. Spatial learning and memory were assessed using a battery of tests, including the Radial arm maze, Multiple T maze and the Morris water maze. Parameters including latency, correct/incorrect decision, reference memory error, and working memory error were determined. The data were analyzed using the Statistical Package for the Social Sciences and considered statistically significant when the P value was ≤ 0.05. The study revealed that acute khat exposure does not have a substantial effect on spatial learning and memory. Except for JWH 133, lone administration of Cannabidiaol and WIN-55,212- 2 resulted in significant enhancement and impairment of cognition, respectively. Whlist, co- administration of khat with cannabinoid agonists attenuates the effect produced by the agonist regardless of the direction of change (enhanced or reduced cognition). Co-administration with antagonists, however, has a pro-cognitive effect. Especially the cannabinoid 1 receptor inveres agonist/antagonist AM251 augmented khat's effect on spatial learning and memory more precisely.en-USKhatEndocannabinoid systemCannabinoid receptor antagonistsCannabinoid receptor agonistsCannabinoid receptorsRadial arm mazeMultiple T mazeMorris water mazeSpatial learning and memory.Thesis