Background: The concurrent use of tramadol and khat has been increasing in Ethiopia, raising concerns about their potential neurocognitive consequences. Despite growing trend, the effects of combined tramadol and khat exposure on learning and memory (LM) have not been previously investigated. Accordingly, the present study was designed to evaluate the impact of co-administration of khat and tramadol on spatial learning and memory in a mouse model.

Materials and Methods: Mice were grouped in four treatments, i.e., control (2% Tween 80), khat (300 mg/kg), tramadol (20 mg/kg), and khat and tramadol co-administered (300 mg/kg and 20 mg/kg, respectively). The Morris Water Maze (MWM) model was used to assess spatial LM. The data were analyzed, and a p-value <0.05 was considered statistically significant.

Results: In the acquisition phase, all groups improved in the ability to detect the hidden platform that training days had a significant effect, [F (3,26) =3.256, p<0.05]. Compared to the controls, the tramadol-treated group showed significantly longer escape latencies on Day 1 (p<0.05). Based on short-term memory (STM) tests, all treatment groups spent less time in the target quadrant (NW) than the control group (p<0.001). In long-term memory (LTM), the control group spent significantly more time in the NW quadrant (42.6±3.8 s) compared with the khat (27.4±4.2 s), tramadol (25.7±3.9 s), and combination groups (18.1±3.1 s) (p<0.001). The khat-treated group showed a significant difference compared to the combined khat- and tramadol-treated group (p<0.01).

Conclusion: The present study assessed the acute effects of khat, tramadol, and their combination on mice spatial memory using the Morris Water Maze. Tramadol impaired initial learning, and all treatments caused short- and long-term memory deficits, with the combination producing the greatest long-term impairment, suggesting additive or synergistic effects on hippocampal-dependent memory.

Khat, Tramadol, Morris Water Maze, Murine, Learning and memory