Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity

Frontiers in Pharmacology

Petri Hyytiä¹  Esko Kankuri¹  Esa R. Korpi¹  Mateusz Dudek¹  Elena de Miguel¹  Essi Törrönen¹  Milo Grotell¹  Bjørnar den Hollander¹  Mikko I. Kettunen²  Jouni Ihalainen³  Markus M. Forsberg³  Aaro Jalkanen³ 

[1] Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;Kuopio Biomedical Imaging Unit, A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland;School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland;

关键词: stimulant;    ethanol;    co-consumption;    MEMRI;    golgi-staining;    methamphetamine;   

DOI  :  10.3389/fphar.2021.679759

来源: DOAJ

【 摘 要 】

Mephedrone (4-MMC), despite its illegal status, is still a widely used psychoactive substance. Its effects closely mimic those of the classical stimulant drug methamphetamine (METH). Recent research suggests that unlike METH, 4-MMC is not neurotoxic on its own. However, the neurotoxic effects of 4-MMC may be precipitated under certain circumstances, such as administration at high ambient temperatures. Common use of 4-MMC in conjunction with alcohol raises the question whether this co-consumption could also precipitate neurotoxicity. A total of six groups of adolescent rats were treated twice daily for four consecutive days with vehicle, METH (5 mg/kg) or 4-MMC (30 mg/kg), with or without ethanol (1.5 g/kg). To investigate persistent delayed effects of the administrations at two weeks after the final treatments, manganese-enhanced magnetic resonance imaging brain scans were performed. Following the scans, brains were collected for Golgi staining and spine analysis. 4-MMC alone had only subtle effects on neuronal activity. When administered with ethanol, it produced a widespread pattern of deactivation, similar to what was seen with METH-treated rats. These effects were most profound in brain regions which are known to have high dopamine and serotonin activities including hippocampus, nucleus accumbens and caudate-putamen. In the regions showing the strongest activation changes, no morphological changes were observed in spine analysis. By itself 4-MMC showed few long-term effects. However, when co-administered with ethanol, the apparent functional adaptations were profound and comparable to those of neurotoxic METH.

【 授权许可】

Unknown