Catha edulis Forsk (khat) reduces spontaneous and rewarded alternation in female mice

Abstract

Around 10 million people chew the fresh leaves and twigs of Catha edulis Forsk (khat), which synthesize cathinone, for its psychostimulatory effect. Several studies have reported that regular khat users show executive and cognitive dysfunction, such as impaired inhibitory control and poor performance on memory tests. In this study, the effect of fresh khat extract (100 and 250 mg/kg) on spatial working memory and short-term memory in mice was assessed using spontaneous and rewarded alternation T-maze tests. In the spontaneous alternation test, mice treated with fresh khat extract decreased their spontaneous alternation level to around chance level, and it remained at this level over the 7 days of khat administration and testing. On testing after a 7-day khat free period, the previously khat treated mice showed alternation level above chance but below their pre-khat alternation level. In the rewarded alternation test, acute treatment with khat caused the mice to alternate well below chance level, and then over the next 3 days of khat treatment, the alternation level increased. After a 2 and 9-day khat-free period, the previously khat treated mice alternated above chance level but below their pre-khat level. In both these tests, the mice did not show any position preference before khat treatment; however, during the khat treatment, the mice showed a right side tendency. The results show that khat treatment causes persistent changes in alternation behavior and promotes perseverative behavior, presumably due to its effect on the neural circuits activity and the neurotransmitters and promotion of position preference.

Keywords: Catha edulis; Khat; Perseverative behavior; Rewarded alternation; Spontaneous alternation; Working memory.

Graphical abstract

Fig. 1

a) Spontaneous alternation (mean + sem; n = 10). Khat treatment was given on day 4–10 (black bar). Following the 7-day khat free period, the mice were tested on day 18-20. Two-way repeated measures ANOVA showed that the saline treated group alternated significantly higher than the khat treated groups on days 4-20. Asterisk (*) shows alternation level below chance. b) Position preference rate of female mice for spontaneous alternation T-maze test. (% mean + sem; n = 10). Khat treatment was given on day 4–10 (black bar). A preference rate below 50 % shows right side preference while above 50 % shows a left side preference.

Fig. 2

Rewarded alternation (mean + sem; n = 10). Khat treatment was given on days 1–4 (black bar). Following a 2- and 9-day khat free period, the groups were tested on days 6 and 13. Two-way repeated measures ANOVA showed that the saline treated group alternated significantly higher than khat treated groups on days 1-13. Asterisk (*) shows alternation level below chance. b) Position preference rate of female mice in rewarded alternation T-maze test (% mean + sem; n = 10). Khat treatment was given on days 1–4 (black bar). A preference rate below 50 % shows right side preference while above 50 % shows a left side preference.