Mohd. Rashid Iqbal*, Sudhir Mishra and Yam Nath Paudel


Pregnenolone and its derivatives have been implicated in neuroprotection and enhance NMDA receptor neurotransmission pointing out their therapeutic potential in schizophrenia. This study was aimed to evaluate the effects of pregnelonone sulphate (Preg S) on behavioural changes and markers of oxidative stress induced by ketamine (Ket) in rats. All rats received intraperitoneal (i.p) injection daily for 14 days with different drug treatments viz. Preg S (11.86 mg/kg), risperidone (2 mg/kg/day) alone and in combination with ketamine (30 mg/kg). Different behavioural tests which included elevated plus maze, spontaneous alternation behaviour, locomotor activity tests were performed after 24 hrs of last dosing followed by the estimation of markers of oxidative stress and acetylcholine esterase (AchE) activity in rat’s brain. Ket produced significant changes in behaviour resembling to that of negative symptoms and memory impairment seen in schizophrenic patients. Preg S treated rats spent more time in open arm in elevated plus maze test, decreased percentage alternation and improved locomotor activity as compared to Ket treated rats. The levels of antioxidants such as superoxide dismutase (SOD) and reduced glutathione (GSH) were reduced while thiobarbituric acid reactive substances (TBARS) were elevated. Preg S administration normalized the antioxidant parameters. Preg S improved learning and memory in elevated plus maze, spontaneous alternation behaviour, locomotor activity, decreased AChE activity and reduced oxidative stress. Thus, we may conclude that Preg S offered neuroprotective and antioxidant effect in Ket induced behavioural symptoms.

Keywords: Pregnenolone sulphate, ketamine, neuroprotective, antioxidant, schizophrenia.

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