Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment

1. Effects of morphine sulphate (1.25, 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 non-tolerant 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.