Dizocilpine and reduced body temperature do not prevent methamphetamine-induced neurotoxicity in the vervet monkey: [C-11]WIN 35,428 positron emission tomography studies

[C-11]WIN 35,428 (WIN), a cocaine analog that binds to the dopamine transpo rter (DAT), and positron emission tomography (PET) were used to evaluate th e potential neuroprotective effects of dizocilpine (MK-801) on methamphetam ine (MeAmp) induced neurotoxicity in the striatal dopamine system of the ve rvet monkey. MK-801 (1 mg/kg, i.m.) was administered 30 min prior to a neur otoxic MeAmp dosage for this species (2 x 2 mg/kg, 4 h apart); control subj ects received MeAmp. MK-801 treated subjects were anesthetized by the drug for 6-8 h; throughout that period, a 2-3 degrees C decrease in body tempera ture was measured. At 1-2 weeks post-MeAmp, decreases of similar to 75% in striatal WIN binding were observed for both MK-801/MeAmp and MeAmp subjects . Thus, in this non-human primate species, the combination of MK-801 pretre atment and reduced body temperature did not provide protection from the MeA mp-induced loss of DAT. Further, the absence of an elevated body temperatur e during the acute MeAmp exposure period indicated that hyperthermia, per s e, was not a necessary concomitant of the MeAmp neurotoxicity profile as ha s been previously demonstrated in rodents. These results provide evidence t hat different regulatory factors maintain the integrity of the rodent and p rimate striatal dopamine systems. (C) 1998 Published by Elsevier Science Ir eland Ltd. All rights reserved.