Summary
The behavioural nature of the delayed hyperactivity induced by systemic administration of morphine was studied in rats. Different components of motility induced by morphine with or without naloxone or haloperidol at different times were analyzed by observation and quantified by an Opto Varimex-3 Activity Meter. By this automatic recording system motility was discriminated into horizontal and two different vertical components and the total distance run by each of the rats was quantified by a computer program. Simultaneously the running pattern was recorded by a XY plotter. By means of these recordings, three subsequent phases of behaviour could be recorded after morphine (15 mg/kg i.p.): 1. a depressed phase (akinesia) lasting 1.5–2 h, followed, 2. by an intermediate phase for 1–1.5 h, still dominated by akinesia but interrupted by sudden bursts of hyperactivity. Finally, 3. a hyperactivity phase lasted for 1.5–2 h, characterized by an equal enhancement of locomotor activity and stereotypy. After 30 mg/kg of morphine the hyperactivity was predominantly characterized by locomotor activity and stereotypy and rearing were less prominent than after the smaller dose. Naloxone (2 mg/kg i.p.) given at the beginning of the hyperactivity phase significantly antagonized rearing but not other motility parameters. However, coadministration of naloxone (2 mg/kg i.p.) simultaneously with morphine (15 mg/kg) clearly antagonized akinesia and completely prevented the development of the delayed hyperactivity. Haloperidol (0.2 mg/kg i.p.) at the beginning of the hyperactivity phase clearly antagonized all of the motility parameters seen during this phase.
We conclude 1. that stereotypy and locomotor activity of the hyperactivity phase produced by morphine are not strictly combined since they follow different dose dependencies: locomotor activity increased more after the higher dose of morphine, however, stereotypy and rearing did not. 2. Akinesia and hyperactivity phase might both be triggered by an initial activation of opioid receptors immediately after injection of morphine. However, the hyperactivity phase (being dopamine dependent in all components measured) seems to develop to an opioid receptor independent process as during the hyperactivity phase it can be reversed by haloperidol but not by naloxone anymore.
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Correspondence to U. Havemann-Reinecke at the above address
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Magnus-Ellenbroek, B., Havemann-Reinecke, U. Morphine-induced hyperactivity in rats — a rebound effect?. Naunyn-Schmiedeberg's Arch Pharmacol 347, 635–642 (1993). https://doi.org/10.1007/BF00166947
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DOI: https://doi.org/10.1007/BF00166947