Izawa Jun-ichi, Yamanashi Kaori, Asakura Taro, Misu Yoshimi, Goshima Yoshio
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Eur J Pharmacol. 2006 Nov 7;549(1-3):84-90. doi: 10.1016/j.ejphar.2006.08.031. Epub 2006 Aug 26.
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.
中枢多巴胺系统在甲基苯丙胺、可卡因和尼古丁等精神兴奋剂的作用中起着重要作用。L-3,4-二羟基苯丙氨酸（DOPA）是多巴胺的前体，已被认为是中枢神经系统中的一种神经递质。我们使用体内微透析技术研究了这些精神兴奋剂对清醒大鼠伏隔核壳中DOPA和多巴胺释放的影响。甲基苯丙胺和可卡因会增加细胞外多巴胺水平。甲基苯丙胺（1mg/kg皮下注射）对多巴胺释放的影响与可卡因（10mg/kg腹腔注射）几乎相当。然而，甲基苯丙胺会增加，但可卡因会降低细胞外DOPA水平。在一项行为研究中，甲基苯丙胺（1mg/kg皮下注射）会诱发咀嚼、行走和嗅探行为。与甲基苯丙胺（1mg/kg皮下注射）的作用相比，可卡因（10mg/kg腹腔注射）对这些行为参数的影响较弱。甲基苯丙胺产生的行为变化会被DOPA环己酯（30mg/kg腹腔注射）抑制，DOPA环己酯是一种竞争性DOPA拮抗剂。因此，伏隔核中的内源性DOPA似乎参与了对这些精神运动兴奋剂的行为反应。
