Differential effects of methamphetamine and cocaine on behavior and extracellular levels of dopamine and 3,4-dihydroxyphenylalanine in the nucleus accumbens of conscious rats.
The central dopamine system plays a prominent role in the effect of psychostimulants such as methamphetamine, cocaine and nicotine. l-3,4-Dihydroxyphenylalanine (DOPA), a precursor of dopamine, has been proposed as a neurotransmitter in the central nervous system. We have studied the effects of these psychostimulants on the release of DOPA and dopamine from the nucleus accumbens shell in conscious rats using in vivo microdialysis. Methamphetamine and cocaine increase the extracellular levels of dopamine. The effect of methamphetamine (1 mg/kg s.c.) on the release of dopamine was almost comparable to that of cocaine (10 mg/kg i.p.). However, methamphetamine increases, but cocaine decreases the extracellular levels of DOPA. In a behavioral study, methamphetamine (1 mg/kg s.c.) induced chewing, walking and sniffing behavior. Cocaine (10 mg/kg i.p.) produces weak effects on these behavioral parameters, when compared to the effects of methamphetamine (1 mg/kg s.c.). The behavioral changes produced by methamphetamine are suppressed by DOPA cyclohexyl ester (30 mg/kg i.p.), a competitive DOPA antagonist. Endogenous DOPA in the nucleus accumbens thus appears to be in involved in the behavioral responses to these psychomotor stimulants.
Izawa
Jun-ichi
J
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Yamanashi
Kaori
K
Asakura
Taro
T
Misu
Yoshimi
Y
Goshima
Yoshio
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006120:Grooming / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008409:Mastication / Q000187:drug effects; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D004295:Dihydroxyphenylalanine; D003042:Cocaine; D004298:Dopamine