Production of tolerance and physical dependence in the rat by simple administration of morphine in drinking water.

1 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. 2 The success of this method depends on the initial provision of a 0.1 mg/ml solution of morphine sulphate. 3 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. 4 Daily intake of morphine may be increased by at least about three fold by increasing the drug concentration to 1.2 mg/ml. 5 Oral morphine administration causes only a moderate loss in body weight. 6 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. 7 It is suggested that this simple method of morphine administration is suitable for further biochemical and behavioural studies of the actions of the drug.