Combined Effects of Psychostimulants and Morphine on Locomotor Activity in Mice

Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. This combination appears to produce synergistic effects on behavior at low doses; however, there is little direct evidence that the combination is stronger than either drug alone. Therefore, we inves...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2004, Vol.96(4), pp.450-458
Main Authors: Mori, Tomohisa, Ito, Shinobu, Narita, Minoru, Suzuki, Tsutomu, Sawaguchi, Toshiko
Format: Article
Language:English
Subjects:
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology
Animals
Cocaine
Cocaine - pharmacology
Dopamine
Dopamine receptors
Dose-Response Relationship, Drug
Drug abuse
Drug Synergism
Haloperidol
Haloperidol - pharmacology
Locomotion
Locomotor activity
Male
Methamphetamine
Methamphetamine - pharmacology
Mice
Morphine
Morphine - pharmacology
Motor Activity - drug effects
Nerve endings
Opioids
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Summary:Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. This combination appears to produce synergistic effects on behavior at low doses; however, there is little direct evidence that the combination is stronger than either drug alone. Therefore, we investigated interactions between psychostimulants and morphine on locomotor activity in mice. Low doses of cocaine (5.0 mg/kg) or methamphetamine (0.5 mg/kg) and morphine (10 mg/kg) enhance locomotor activity in a synergistic fashion. Effective doses of cocaine (20 mg/kg) and morphine (20 mg/kg) increased locomotion in an additive fashion. In contrast, combination of methamphetamine (1.0 and 2.0 mg/kg) and morphine (10 and 20 mg/kg) did not merely enhance their effects (or attenuated the peak effects of methamphetamine-induced hyperlocomotion). These results indicate that different mechanisms explain the interaction between morphine and methamphetamine or cocaine. It is well known that psychostimulants- and opioids-induced hyperlocomotion is mediated by the activation of the dopaminergic system, however, haloperidol (a dopamine receptor antagonist) and U50,488H (which attenuates dopamine release from nerve terminals) significantly increased the effects of methamphetamine and morphine on the locomotor activity. These results suggest that excess dopaminergic activation may be involved in the effects of methamphetamine and morphine on locomotor activity in mice.
ISSN:1347-8613
1347-8648
1347-8648
DOI:10.1254/jphs.fpj04039x