Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese.
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 [11C]dihydrotetrabenazine ([11C]DTBZ). After 27 weeks of treatment [11C]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 [11C]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.
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Andres
A
Asser
Department of Pathophysiology, University of Tartu, Tartu, Estonia.
Sulev
S
Kõks
Turku PET Centre, University of Turku, Turku, Finland.
Anniina
A
Snellman
Turku PET Centre, University of Turku, Turku, Finland.
Merja
M
Haaparanta-Solin
Turku PET Centre, University of Turku, Turku, Finland.
Eveliina
E
Arponen
Turku PET Centre, University of Turku, Turku, Finland.
Tove
T
Grönroos
Institute of Gene Technology, Tallinn Technical University, Tallinn, Estonia.
Jaak
J
Nairismägi
Department of Chemistry, Uppsala University, Uppsala, Sweden.
Jonas
J
Bergquist
Department of Biochemistry, University of Tartu, Tartu, Estonia.
Ursel
U
Soomets
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Piret
P
Piip
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Mall
M
Eltermaa
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Martin
M
Sauk
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Hanna
H
Lindmäe
Turku PET Centre, University of Turku, Turku, Finland; Department of Neurology, Turku University Hospital, Turku, Finland.
Juha O
JO
Rinne
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia. Electronic address: pille.taba@kliinikum.ee.
Pille
P
Taba
D000818:Animals; D001345:Autoradiography; D001696:Biomechanical Phenomena; D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005684:Gait / Q000187:drug effects / Q000502:physiology; D013287:Illicit Drugs / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D008345:Manganese / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D049268:Positron-Emission Tomography; D011427:Propiophenones / Q000633:toxicity*; D011619:Psychotropic Drugs / Q000633:toxicity*; D019275:Radiopharmaceuticals; D011897:Random Allocation; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives; D013997:Time Factors; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D011427:Propiophenones; D011619:Psychotropic Drugs; D019275:Radiopharmaceuticals; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; C047806:monomethylpropion; D008345:Manganese; D013747:Tetrabenazine
Ephedrone; Manganism; Methcathinone; PET; VMAT2