Effect of roots aqueous extract of Delphinium denudatum on morphine-induced tolerance in mice
Introduction
The development of physical dependence and tolerance with repeated use is a characteristic feature of all the opioid drugs and represents major limitations in their clinical use. Tolerance and dependence are thought to result from neural adaptions produced by repeated exposure.
The daily administration of morphine or other opioids to rodents in one or more injections per day has been used for many years to produce a tolerant state, which develops at a rate dependent on the specific drug, the dosage schedule, the interval between doses and the sensitivity of pharmacological assay. The signs of tolerance and dependence are measured in tolerant animals by the evocation of abstinence signs by the administration of a narcotic antagonist.
Delphinium denudatum, Wall (Dd) (Jadwar, Family: Ranunculaceae), is a plant reputed in the Indian system of medicine (Unani medicine) to be useful in the management of nervous disorders and opium addiction [1], [2].
Recent studies have demonstrated that Dd possesses anticonvulsant properties in rats [3], [4]. Investigations on Dd revealed its beneficial effects in cardioprotection [5], [6], hepatoprotection [7] and immunomodulation [8]. Recently, it has been reported that Jawahar Mohra (JM), a compound formulation of Unani medicine containing Dd, has been showing antistress activity [9]. The present experiments were undertaken to study the protective effect of Dd aqueous root extract on the development of tolerance and dependence to morphine in mice.
Section snippets
Drugs
The roots of D. denudatum, Wall were procured from Khari Bavli market of Delhi, India, in August 1997, and air-dried. The plant material was identified by Dr M.P. Sharma at the Department of Botany, Faculty of Science, Hamdard University, New Delhi-110062, where a voucher specimen has been deposited. The aqueous extract of the roots was obtained by the help of soxhlet's apparatus. The yield of the extract was 30% w/w in terms of dried starting material. Morphine sulfate (Narcotic division,
Results and discussion
The oral administration of D. denudatum roots aqueous extract from 200 to 1600 mg/kg showed an inhibition on naloxone-induced withdrawal by 16.82 to 75.50% (Table 1). The mechanism of this observed inhibition remains unclear.
In a previous paper, an anti-addictive profile of a compound Unani formulation—a safe analgesic polyherbal preparation containing Dd as one of the components—has been reported [11], [12]. The present study shows that its anti-addictive profile could be mainly due to the
Acknowledgements
The supply of morphine sulfate (Narcotic division, Ghazipur, India) by Dr S.B. Vohora (HOD.) Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, is acknowledged.
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