Neurotoxicity in dopamine and 5-hydroxytryptamine terminal fields: a regional analysis in nigrostriatal and mesolimbic projections.
In summary, we have shown that MA is toxic to both 5-HT and DA cells and we have proposed a mechanism that would account for this response, namely, the conversion of the transmitters to neurotoxins. In addition, brain depletions of DA seem regionally specific with larger depletions occurring in some areas than in others. The depletions, however, do not seem to depend entirely on the nuclei of origin, that is, substantia nigra versus VTA. 5-HT was depleted by different amounts in the various regions examined and the 5-HT depletions, although proportional to the DA depletions, were consistently greater. The reasons for this differential sensitivity of the 5-HT and DA systems to the toxic effect of MA is speculative, but may be related to the differential formation of toxins due to the differing availability of oxygen and superoxides at serotonergic and dopaminergic synapses.
Seiden
L S
LS
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Commins
D L
DL
Vosmer
G
G
Axt
K
K
Marek
G
G
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology / Q000633:toxicity*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D012701:Serotonin; D008694:Methamphetamine; D000661:Amphetamine; D004298:Dopamine