Inhibitory and stimulatory effects of morphine on locomotor activity in mice: biochemical and behavioral studies.
A possible interaction between the opposite effect (inhibition and stimulation) of morphine on locomotor activity in mice and monoaminergic systems in the striatum was studied. Ten minutes after systemic administration, morphine at 1.25 mg/kg decreased locomotor activity and the levels of 3-methoxytyramine (3-MT), whereas at 20 mg/kg locomotor activity and 3-MT levels increased. At the same time, no change in the other monoamine metabolite (DOPAC, HVA, MHPG, and 5-HIAA) levels was observed. Sixty minutes after administration, morphine at 1.25 mg/kg did not induce any change in locomotor activity or in all the monoamine metabolite levels measured. On the other hand, morphine at 20 mg/kg maintained an initial increase in locomotor activity and increased not only 3-MT levels, but also other metabolite (DOPAC, HVA, MHPG, and 5-HIAA) levels. These results suggest that, at low dosages, the inhibitory effect of morphine on locomotor activity in mice may be related to a decrease of the presynaptic dopamine release in the striatum and that the stimulatory effect of morphine, at high dosages, may be related to an increase of the presynaptic dopamine release in the striatum.
Saito
H
H
Department of Pharmacology, School of Dentistry, Iwate Medical University, Morioka, Japan.
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology; D012701:Serotonin / Q000502:physiology
D015306:Biogenic Monoamines; D012701:Serotonin; D009020:Morphine; C001746:3-methoxytyramine; D004298:Dopamine; D009638:Norepinephrine