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Combined effects of psychostimulants and morphine on locomotor activity in mice.

Abstract：

: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.

journal_name

J Pharmacol Sci

journal_title

Journal of pharmacological sciences

authors

Mori T,Ito S,Narita M,Suzuki T,Sawaguchi T

doi

10.1254/jphs.fpj04039x

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

450-8

issue

4

eissn

1347-8613

issn

1347-8648

pii

JST.JSTAGE/jphs/FPJ04039X

journal_volume

96

pub_type

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