• Khat is a widely used plant-based psychostimulant. • Administration of khat leads to disruption of spatial working memory in mice. • It promotes in mice perseverative behavior rather than alternation behavior. • Khat treated mice also show right side position preference.

Khat (Catha edulis Forsk), the natural source of cathinone and other psychoactive agents, is chewed by millions of persons in eastern Africa and the Arabian Peninsula for its psychostimulant effect. Using the conditioned place preference paradigm, this study tested fresh khat extract for place preference induction, extinction, and reinstatement. Female mice treated with 100 and 250 mg/kg of khat extract showed conditioned place preference, which was extinguished following a 16-day khat-free period. However, the place preference was reinstated following the first priming dose of the khat extract but not with the second priming dose done 35 days after the last conditioning treatment. The results show that khat has a rewarding/reinforcing property and can also lead to relapse behavior in persons attempting to stop khat use.