Significance of biogenic amines for opioid-induced locomotor activity in rats

The effect of the opioid levorphanol on locomotor activity was investigated in rats treated with p-chlorophenylalanine (PCPA) or 6-hydroxydopamine (6-OHDA). Acute oral administration of 10 or 30 mg/kg levorphanol induces a time- and dose-dependent alteration in motility. Ingestion of 10 mg/kg levorphanol in rats with an intact biogenic amine content results in an increase of locomotion for 180 min followed by a longer lasting, small but significant, reduction of motor activity. The course of motility after 30 mg/kg is similar to that after 10 mg/kg, but the initial peak appears after a 3-h delay. In 5-hydroxytryptamine (5-HT)-deficient rats, the first excitation of motility is enhanced and its subsequent depression intensified. After administration 30 mg/kg a general reduction in motor activity occurs. The effect of 10 mg/kg levorphanol after 6-OHDA treatment is on a lower level, similar to that of rats with intact amine content. After 30 mg/kg levorphanol an immediate and longer lasting increase in activity appears. Chronic ingestion of about 40 mg/levorphanol/kg per day enhances the total amount of activity in normal rats as well as in animals with catecholamine (CA) depletion, but not in those treated with PCPA. In all cases, withdrawal of the opioid results in a reduction of activity below that of control levels.