Interaction of Catha edulis (Vahl) Forssk. ex Endl. (Khat) and the Endocannabinoid system on spatial learning and memory in mice
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Date
2023
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Addis Ababa University
Abstract
Numerous 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.
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Keywords
Khat, Endocannabinoid system, Cannabinoid receptor antagonists, Cannabinoid receptor agonists, Cannabinoid receptors, Radial arm maze, Multiple T maze, Morris water maze, Spatial learning and memory.