Complicated interaction between psychostimulants and morphine in expression of phenotype of behavior in the dopaminergic system of BALB/c mice.
It is believed that BALB/c mice appear to be less sensitive to the locomotor effects of abused drugs compared to other strains, and several behaviors induced by abused drugs depend on genetic factors. The present study was designed to investigate the effects of the interaction between psychostimulants and morphine on behavior in BALB/c mice. Morphine and cocaine induced hyperlocomotion and hypolocomotion, respectively, while methamphetamine did not affect locomotor activity and high doses of methamphetamine significantly increased self-injurious behavior. Cocaine or methamphetamine increased the effects of morphine on locomotor behavior. Haloperidol (a dopamine-receptor antagonist) attenuated the hyperlocomotion induced by the combination of cocaine or methamphetamine plus morphine. These results indicate that the synergistic effects of methamphetamine or cocaine and morphine on locomotor activity are mediated through enhancement of the dopaminergic system and that combinations of psychostimulants and morphine enhance the locomotor activity in BALB/c mice. On the other hand, morphine completely attenuated methamphetamine-induced self-injurious behavior. Furthermore, a low dose (0.01 mg/kg) of haloperidol significantly increased the effects of methamphetamine and morphine on the locomotor activity. Hyperlocomotion induced by psychostimulants is mediated by the mesolimbic dopaminergic system, whereas stereotyped behaviors is mediated by the nigrostriatal dopaminergic system. Our findings suggest that balances of the activation of dopaminergic neurons (between mesolimbic and nigrostriatal systems) may play an important role to engender corresponding behavioral outcomes in BALB/c mice.
Department of Legal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Shinobu
S
Ito
Tomohisa
T
Mori
Mizuho
M
Namiki
Tadashi
T
Suzuki
Toshiko
T
Sawaguchi
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006220:Haloperidol / Q000008:administration & dosage / Q000633:toxicity; D008032:Limbic System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D008694:Methamphetamine; D009020:Morphine; D003042:Cocaine; D006220:Haloperidol; D004298:Dopamine