Delta opioid peptide [d-Ala2, d-Leu5] enkephalin blocks the longterm loss of dopamine transporter induced by multiple administration of methamphetamine: involvement of opioid receptors and reactive oxygen species

Delta opioid peptide [D-Ala2,D-leu5]enkephalin (DADLE) can prolong organ preservation and increases myocardial tolerance to ischemia. Our study examined the protective property of DADLE against methamphetamine- (METH) induced dopami-nergic terminal damage in the central nervous system. Because the neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30 min before each METH administration (5 or 10 mg/kg, i.p., four injections in a day at 2-hr intervals), dose-dependently blocked the METH-induced long-term dopamine transporter loss. The opioid an-tagonist naltrexone blocked this action of DADLE in both as-pects of striata but tends not to affect the effects of DADLE in the nucleus accumbens. DADLE did not alter changes in bod