Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers

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Asser , A , Hikima , A , Raki , M , Bergström , K , Rose , S , Juurmaa , J , Krispin , V , Muldmaa , M , Lilles , S , Rätsep , H , Jenner , P , Köks , S , Männistö , P T & Taba , P 2020 , ' Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers ' , Journal of Neural Transmission , vol. 127 , no. 5 , pp. 707-714 . https://doi.org/10.1007/s00702-019-02110-z

Title: Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers
Author: Asser, Andres; Hikima, Atsuko; Raki, Mari; Bergström, Kim; Rose, Sarah; Juurmaa, Julius; Krispin, Villem; Muldmaa, Mari; Lilles, Stella; Rätsep, Hanna; Jenner, Peter; Köks, Sulev; Männistö, Pekka T.; Taba, Pille
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Divisions of Faculty of Pharmacy
Date: 2020-05
Language: eng
Number of pages: 8
Belongs to series: Journal of Neural Transmission
ISSN: 0300-9564
URI: http://hdl.handle.net/10138/318870
Abstract: An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced I-123-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man.
Subject: Methcathinone
Ephedrone
Manganese
Nigrostriatal damage
DOPAMINE
EPHEDRONE
EXPOSURE
ADDICTS
BINDING
3112 Neurosciences
317 Pharmacy
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