Axt K J, Commins D L, Vosmer G, Seiden L S
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Brain Res. 1990 May 7;515(1-2):269-76. doi: 10.1016/0006-8993(90)90606-c.
Depletion of brain dopamine (DA) by pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMT) has been shown to prevent the long-term neurotoxic effects of methamphetamine (MA). In addition, it has recently been reported that the neurotoxins 6-hydroxydopamine (6-OHDA) and 5,6-dihydroxytryptamine (5,6-DHT) are formed endogenously in neostriatum and hippocampus, respectively, following a single neurotoxic dose of MA. We, therefore, have examined the ability of AMT pretreatment to prevent the MA-induced formation of 6-OHDA and 5,6-DHT. We report that AMT pretreatment significantly decreases the frequency with which 6-OHDA and 5,6-DHT are detected following MA administration. Neurotoxin formation is compared with brain levels of DA and 5-hydroxytryptamine (5-HT) 2 weeks after MA administration. It is concluded that the ability of AMT to attenuate both 6-OHDA formation and long-term depletions of DA is due to a decrease in the MA-releasable pool of DA. The effect of AMT on MA-induced depletions of 5-HT is less clear and may involve additional factors.
