PRODUCTION OF TOLERANCE AND PHYSICAL DEPENDENCE IN THE RAT BY SIMPLE ADMINISTRATION OF MORPHINE IN DRINKING WATER

Abstract

Rats are capable of consuming solutions of morphine sulphate in drinking water ad libitum in the absence of taste‐masking chemicals and without the need for scheduled provision or prior parenteral administration of the drug. The success of this method depends on the initial provision of a 0.1 mg/ml solution of morphine sulphate. When the drug concentration is increased to 0.4 mg/ml, the rats achieve an average daily intake of 50 mg/kg body wt. each. Daily intake of morphine may be increased by at least about three fold by increasing the drug concentration to 1.2 mg/ml. Oral morphine administration causes only a moderate loss in body weight. Rats whose daily intake of the drug is 50 mg/kg exhibit tolerance to the analgesic action of morphine and show a drastic loss in body weight at 24 h after withdrawal and most of the behavioural symptoms of the naloxone‐precipitated withdrawal syndrome. It is suggested that this simple method of morphine administration is suitable for further biochemical and behavioural studies of the actions of the drug. 1982 British Pharmacological Society