LOWERING AMBIENT OR CORE BODY-TEMPERATURE ELEVATES STRIATAL MPP-TREATED MICE( LEVELS AND ENHANCES TOXICITY TO DOPAMINE NEURONS IN MPTP)

The neuroprotective effects of lowering body temperature have been wel l documented in various models of neuronal injury. The present study i nvestigated the effects a lower ambient or core body temperature would have on damage to striatal dopamine (DA) neurons produced by 1-methyl -4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice received systemic MP TP treatment at two different temperatures, 4 degrees C and 22 degrees C. MPTP-treated mice maintained at 4 degrees C demonstrated (1) a gre ater hypothermic response, (2) a significant reduction in striatal DA content and tyrosine hydroxylase (TH) activity, and (3) significantly greater striatal 1-methyl-4-phenylpyridinium (MPP+) levels, as compare d to mice dosed with MPTP at room temperature. Parallel studies with m ethamphetamine (METH) were conducted since temperature appears to play a pivotal role in the mediation of damage to DA neurons by this CNS s timulant in rodents. As previously reported, METH-induced hyperthermia and the subsequent loss of striatal DA content were attenuated in ani mals dosed at 4 degrees C. We also evaluated the effects a hypothermic state induced by pharmacological agents would have on striatal neuroc hemistry and MPP+ levels following MPTP treatment. Concurrent administ ration of MK-801 or 8-OHDPAT increased the striatal MPP+ levels follow ing MPTP treatment. However, only 8-OHDPAT potentiated the MPTP-induce d decrements of striatal DA content and TH activity; MK-801 did not af fect MPTP decreases in these striatal markers of dopaminergic damage. Altogether, these findings indicate that temperature has a profound ef fect on striatal MPP+ levels and MPTP-induced damage to DA neurons in mice. (C) 1998 Elsevier Science B.V.