Reversal of Scopolamine-Induced Deficits in Navigational Memory Performance by the Seed Oil of Celastrus paniculatus

Abstract

Celastrus paniculatus (CP), a medicinal plant from India has been reputed to be useful as a pharmaceutical aid for learning and memory. We investigated the effects of the seed oil of CP on the 6 day performance of young adult rats in a navigational memory task--the Morris water maze. Chronic oral (gavage) daily treatment with CP, (50, 200, or 400 mg/kg) for 14 days completely reversed the scopolamine (0.5 mg/kg)-induced task performance deficit. On the other hand, acute treatment (single injection prior to scopolamine treatment) with CP (200 mg/kg) did not significantly reverse the scopolamine-induced impairment in maze performance. Alone, CP produced a slight, but significant improvement in maze performance on the first day of testing. Acute treatment or chronic 14 day treatment with CP resulted in no significant alteration in normal locomotor activity in an open field. Moreover, CP did not alter the scopolamine-induced increases in locomotor activity. Chronic treatment with CP did not alter brain acetylcholinesterase levels and no signs of cholinergic overstimulation were ever noted during or after treatment. Thus, the seed oil of CP, when administered chronically, selectively reversed the impairment in spatial memory produced by acute central muscarinic receptor blockade, supporting the possibility that one or more constituents of the oil may offer cognitive enhancing properties. The neural mechanism underlying the reversal of scopolamine’s mnemonic effects by CP is not yet known, but it is not related to an anticholinesterase-like action.

Introduction

TRADITIONAL or folk medicines have been widely employed for centuries, and they remain one important source for the discovery of new bio-active compounds. Ayurveda, an ancient traditional system of medicine that has been practiced in India since 200 B.C. employs a large number of medicinal plants used in the prevention and treatment of a wide number of diseases. One of these includes the plant Celastrus paniculatus Willd. (CP), a plant known for centuries as “the elixir of life”. According to Ayurveda, depending upon the dose regimen, CP may be employed as a stimulant-nerve tonic, rejuvenant, sedative, tranquilizer and diuretic. It is also used in the treatment of leprosy, leucoderma, rheumatism, gout, paralysis and asthma. Most of the claims for this plant have not been substantiated in rigorous scientific settings. This includes the purported property of CP germane to this study—its ability to stimulate the intellect and sharpen the memory. There have been pharmacological studies to suggest that the oil obtained from the seeds of CP possess sedative and anticonvulsant properties 15, 17. Sheath and coworkers [33]isolated an active fraction of the oil that they termed Mal-IIIA, and suggested that this component exhibits the sedative and tranquilizing effects observed in rats and mice. Sporadic reports in the scientific literature also exist to suggest that the neet oil of CP or its extracts exhibit the following pharmacological actions: anti-viral [7], anti-bacterial [28], analgesic [2], anti-inflammatory 2, 11, anti-malarial [5], anti-fatigue [19], anti-spermatogenic [36], insecticidal [4], hypolipemic [22], and, potentiation of barbiturate sleeping time [3]. The indigenous peoples that employ CP also know this preparation as a general cognitive enhancing agent. Several reports are now available to support this later notion in the laboratory setting. Karanth and coworkers [20], and Nalini and coworkers [26], reported that rats treated with CP improved their performance in raised platform shock-avoidance paradigm and two-way passive avoidance paradigm, respectively. Nalini and coworkers [25]reported that chronic treatment with CP oil produced improvement in I.Q. scores and decreased the content of catecholamine metabolites, vanilylmandelic acid and homovanillic acid in the urine of mentally retarded children. Similar neurochemical results were also observed in rats, wherein chronic treatment with CP decreased the brain content of norepinephrine, dopamine, and serotonin, and decreased their respective metabolites in the brain and urine [26].

Pharmacologic blockade of central muscarinic receptors produces a short-term amnestic response in a wide variety of animal models performing a variety of tasks challenging learning and recall 13, 14, 16, 23. Scopolamine is particularly effective when administered just before task training [13]. One of the most widely employed paradigms used to assess working memory in rodents is the Morris water maze spatial navigational task [24]. Administration of low doses of scopolamine have been shown to effectively interfere with task performance. One other advantage of the use of scopolamine is that the drug evokes characteristic changes in locomotor activity in an open field 1, 29, 32, 35. The effects of scopolamine on maze performance and locomotor activity can be reversed by the administration of classical (centrally-acting) muscarinic receptor agonists, particularly inhibitors of acetylcholinesterase [32]. Thus, the seed oil of CP was examined for its ability to reverse the effects of either or both the scopolamine-induced impairment of water maze performance and increased open field locomotor activity in adult rats. We also determined whether in vivo administration of CP could inhibit brain acetylcholinesterase activity measured ex vivo.