Catha edulis F. (Khat) Reverses Haloperidol But Not Morphine Induced Motor Deficits Following Acute and Subacute Administration in Mice

Abstract

Khat (Catha edulis F.) is widely chewed in Africa and the Middle East. The use of the plant is associated with different central and peripheral effects. The aim of this study is to evaluate acute and subacute effects of crude khat extract in haloperidol and morphine-pretreated mice by measuring behavioural and biochemical parameters. Crude khat extract obtained using a mixture of chloroform and diethyl ether (1:3) was administered orally in doses of 100, 200 and 300 mg/kg as a single dose and repeatedly for fourteen days, and motor parameters, including catalepsy and locomotor behaviour as well as biochemical markers for oxidative stress, such as activity of superoxide dismutase (SOD) were measured. Whilst acute and subacute oral administration of khat failed to reverse morphine-induced motor deficits, it was capable of reversing the haloperidol-induced one in a manner that depended on time and dose. In both settings, khat at 200 and 300 mg/kg dose as well as amphetamine (50 mg/kg) produced a consistent improvement in motor performance. The effects observed were either comparable or better than amphetamine. By contrast, both khat (300 mg/kg) and amphetamine increased plasma SOD activity in both haloperidol and morphine pretreated animals. SOD activity increase was significantly higher in khat 300 mg/kg compared to haloperidol/morphine pretreated controls (p<0.001) as well as amphetamine treated (p<0.05) mice. The findings collectively indicate that haloperidol induced motor abnormalities are mediated by the dopaminergic system, while morphine may utilize other pathways in causing such deficits. Moreover, modulation of SOD although considered to be a contributing factor in reversing haloperidol-induced motor deficit, it might not be sufficient to prevent that induced by morphine.

Keywords: Catha edulis, motor activity, superoxide dismutase, haloperidol, morphine