Combined Effects of Psychostimulants and Morphine on Locomotor Activity in Mice

Abstract

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.

Complicated Interaction Between Psychostimulants and Morphine in Expression of Phenotype of Behavior in the Dopaminergic System of BALB/c Mice

“…In fact, hyperlocomotion-induced by methamphetamine (2.0 mg / kg) was attenuated by its combination with morphine (10 or 20 mg / kg) in ddY mice (12), unlike in the case of BALB / c mice. In another recent study, it was that the co-administration of a µ-opioid receptor agonist and cocaine increased extracellular dopamine levels in the nucleus accumbens as measured by microdialysis techniques (28).…”

“…15 min prior to the administration of methamphetamine or cocaine plus morphine. The doses and the pretreatment time were based on our previous papers (12,21). The doses of methamphetamine were selected based on our previous papers (13) indicating that methamphetamine induced hyperlocomotion and self-injurious behaviors in ddY mice.…”

“…On the other hand, previous studies demonstrated that some opioid receptor agonists have an antagonistic effect on the dopamine-related behavior, especially stereotyped behaviors, in mice (15 -17). We interestingly demonstrated that haloperidol (a dopaminereceptor antagonist) increased the locomotor activity on combined effects of psychostimulants (methamphetamine and cocaine) and reduced methamphetamine-induced self-injurious behavior accompanied by an induction in increase of locomotor activity (12,13). Thus, the mechanism(s) for expression of the phenotype of dopamine-related behavior induced by combination of psychostimulants and opioids in mice is not clear.…”

“…Combining psychostimulants and morphine or heroin could enhance their locomotor-activating and rewarding effects in rodents (6,9,12,14,15). Furthermore, Suzuki et al (10,11) previously demonstrated that morphine could enhance the discriminative stimulus effects of cocaine.…”

Intake of Fermented Soybean (Natto) Increased Locomotor Activity in Mice

“…In the open field test, nattofed mice showed enhanced ambulation count compared to control (unpublished data). Therefore, in this study, we examined (i) the effects of natto on mouse locomotor activity 14 d after feeding and (ii) which receptor was involved in the enhancement of locomotor activity by natto granules using haloperidol (a dopamine receptor antagonist) 5) and methysergide (a serotonin (5-HT) 1/2 receptor antagonist). 6) …”