Behavioural changes and development of tolerance to repeated administration of khat (Catha edulis Forsk) in mice

Abstract

Abstract: Khat use is showing an increase in many countries, including Ethiopia. Khat leaves are chewed for their euphoric effect, to guard off tiredness, and with the assumption that chewing khat facilitates learning. Although most research done so far employed cathinone, the major amphetamine-like CNS stimulant alkaloid contained in khat leaves, it is known that there are more than 20 pharmacologically active compounds in the leaves. Moreover, results from experiments where cathinone alone was given parenterally to experimental animals may not wholly reflect the behavioural toxicity observed after administering khat in a dosage similar to that used traditionally. This work was undertaken to study how repeated ingestion of khat affects memory processes and whether tolerance or sensitization develops in the process. The oral adminstration of an aqueous suspension of khat leaves for one week to mice produced a significant impairment of memory between days two and five of repeated dosing in an active avoidance test (p<0.001; Studient’s paired t=test). Results from the passive avoidance test showed a similar pattern of impairment of memory. Likewise, repeated administration of khat suspension produced a significant decrease in locomotor activity on days three and four of repeated dosing (p<.001 p<0.01, respectively). The decrease in locomotor activity was not accompanied by stereotyped behaviour, possibly indicating that, at the dose employed, khat leaves may be devoid of a pronounced 5-HT-releasing action. These findings, together with that from the rotarod test, suggest that acute tolerance, rather than sensitization, develops during sub-acute khat administration. The disruption in memory processes and performance caused by khat is short-lived and values returned to baseline levels within a week. It is inferred that people, such as students and drivers who have started to use khat, could display memory impairment, which in turn may adversely affect their performance. [Ethiop. J. Health Dev. 1998;12(3):253-260]