The neuropsychopharmacological effects of Catha edulis in mice offspring born to mothers exposed during pregnancy and lactation

Abstract

Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat during pregnancy, data are sparse with regard to the consequences of long-term exposure during pregnancy and lactation. The present work, therefore, was initiated to evaluate the neuropsychopharmacological effects of Catha edulis exposure during pregnancy and lactation in mice at postnatal day 28. To this effect, a lyophilized extract of khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water (negative control, CONT) were administered daily to pregnant mice from gestational day 6 until weaning. Neuropsychopharmacological measurements were done by making use of a battery of neurobehavioural and cognitive tests. Moreover, toxicity to liver and kidney was also evaluated by determining biochemical markers for possible tissue damage. K200 produced significant motor in-coordination and emotional instability; as revealed by impairment in both cliff avoidance (p < 0.01) and forelimb grip strength (p < 0.001), as well as by an increase in stereotyped behaviour such as grooming (p < 0.05), and in the percent of time spent in open arms (p < 0.05). On the other hand, K100 had an effect only on grip strength where a decrement was noted (p < 0.01). A different pattern emerged with AMP whilst it increased duration of sniffing (p < 0.05), neither grip strength nor the time spent in the open arm was affected compared with CONT. Increased latency to reach the goal box and the number of wrong decisions (p < 0.05) in both the learning and the recall tests was observed with K200 and AMP. By contrast, both doses of khat and AMP equally affected performance in the Y-maze (p < 0.05). Alterations in the biochemical indices of liver and kidney function were also noted with AMP and K200. These findings indicate that khat exposure produces dose-related central and peripheral effects during pregnancy and lactation which might pose a serious impediment to the physical and mental development of the offspring.