Summary1. Effects of morphine sulphate (1P25, 2 5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in nontolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effect. 2. The same doses of morphine were administered daily for 30 days. No tolerance developed within this time to the excitatory effect. The locomotor excitatory effect of the higher three doses of morphine became progressively more pronounced over treatment periods of 30 days (and 48 days for 20 mg/kg), while the latency to peak activity decreased.3. An explanation of these results is suggested on the basis of two different central drug-receptor interactions affecting motility.

A double-blind therapeutic trial of azathioprine in 20 patients with acute proctocolitis was performed over a 3-month period. Azathioprine was compared with sulfasalazine in patients paired and treated in a sequential order. Clinical, laboratory, endoscopic, biopsy, and radiologic data were assessed by semiquantitative criteria. No significant difference in the effect of the drugs was observed. Both azathioprine and sulfasalazine produce significant improvement in clinical symptoms, some laboratory findings (ESR, serum iron), and endoscopic and biopsy findings (P smaller than 0.05). Radiologic improvement was less evident (P smaller than 0.10). On the overall final evaluation of the trial, 14 patients were improved, and 6 remained stationary or worsened (P smaller than 0.10). This short-term trial confirms previous uncontrolled experiences of one of the authors on larger series of patients.

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Male Sprague Dawley rats were injected daily with saline (morphine naive rats) or 20 mg/kg morphine (morphine experienced rats), starting at least 12 days before training. Subsequent place and taste conditioning indicated that 2.5 mg/kg morphine caused a significant increase in the amount of time spent on the least preferred side by morphine experienced but not by morphine naive rats; furthermore, saccharin consumption was markedly decreased and slightly increased by 10-20 mg/kg morphine in naive and experienced rats, respectively. It was concluded that morphine experience enhances the reinforcing efficacy of morphine and broadens the conditions under which the drug is reinforcing; thus it possibly increases morphine abuse potential.