1. Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese.
- Author
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Asser A, Kõks S, Snellman A, Haaparanta-Solin M, Arponen E, Grönroos T, Nairismägi J, Bergquist J, Soomets U, Piip P, Eltermaa M, Sauk M, Lindmäe H, Rinne JO, and Taba P
- Subjects
- Animals, Autoradiography, Biomechanical Phenomena, Carbon Radioisotopes, Central Nervous System Stimulants toxicity, Corpus Striatum diagnostic imaging, Corpus Striatum metabolism, Disease Models, Animal, Gait drug effects, Gait physiology, Illicit Drugs toxicity, Injections, Intraperitoneal, Male, Mice, Inbred C57BL, Motor Activity drug effects, Motor Activity physiology, Positron-Emission Tomography, Radiopharmaceuticals, Random Allocation, Substance-Related Disorders diagnostic imaging, Tetrabenazine analogs & derivatives, Time Factors, Corpus Striatum drug effects, Manganese toxicity, Propiophenones toxicity, Psychotropic Drugs toxicity, Substance-Related Disorders metabolism, Vesicular Monoamine Transport Proteins metabolism
- Abstract
Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [
11 C]dihydrotetrabenazine ([11 C]DTBZ). After 27 weeks of treatment [11 C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [11 C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate., (Copyright © 2016 Elsevier B.V. All rights reserved.)- Published
- 2016
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