Effects of methionine-enkephalin and morphine on spontaneous locomotor activity: Antagonism by naloxone

Methionine-enkephalin (MEK), a postulated endogenous ligand for the opiate receptors, when administered intracerebroventricularly (ICV) in a dose of 1.75 μmoles/kg) of morphine sulfate had no effect on motor activity. Higher doses (7.0 μmoles/kg) of both MEK and morphine produced profound depression in motor activity; the decrease was significant from 6 to 30 min after their administration. Subcutaneous administration of naloxone (1 mg/kg) did not alter the motor activity. However, administration of naloxone (1 mg/kg) 2 min prior to MEK (7.0 μmole//kg) administration completely blocked the effect of the latter for 15 min while antagonizing the effect of 7.0 μmoles/kg of morphine for 10 min. At 30 min after 7.0 μmoles/kg of either MEK or morphine administration, the motor activity in these groups was identical with that of the naloxone treated group. Methionine-enkephalin in doses of 0.2 and 0.4 μmole/kg had no effect on motor activity for 1 hr observation period. A significant increase in motor activity was recorded 45 and 60 min after 0.2 μmole/kg of morphine sulfate, whereas 0.4 μmole/kg dose of morphine showed significant increase in motor activity only at 60 min after its administration. Furthermore, 0.2 μmole/kg of morphine produced a greater increase in motor activity compared with 0.4 μmole/kg dose at 45 and 60 min after administration. It is concluded that morphine and MEK produce differential effects on mouse spontaneous motor activity with respect to time and dose and that naloxone can inhibit the effects of MEK more effectively than that of morphine on motor activity.