Behavioral activating effects of opiates and opioid peptides

Locomotor activity of rats and mice was monitored following administration of the opiates, morphine, methadone, and etonitazene, or the opioid peptides, beta-endorphin, D-Ala2-Met5-enkephalinamide, and D-Met2-Pro5-enkephalinamide. In rats these agents produced dose-related biphasic patterns of activity consisting of an initial depression in locomotion followed by a period of hyperactivity. Intravenous administration of morphine, methadone, or etonitazene in mice produced dose-related increases in stereotyped locomotor activity. The metabolically resistant enkephalin analog, D-Met2-Pro5-enkephalinamide induced a similar pattern of effects. However, doses of beta-endorphin up to 20 mg/kg, iv, failed to elicit locomotor stimulation in mice. The similarity in the naloxone-reversible responses induced by opiates and certain opioid peptides suggests that the same underlying mechanisms may subserve their behavioral effects.