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.