title: Manganese-enhanced magnetic resonance imaging reveals differential long-term neuroadaptation after methamphetamine and the substituted cathinone 4-methylmethcathinone (mephedrone).
abstract: BACKGROUND
  In recent years there has been a large increase in the use of substituted cathinones such as mephedrone (4-methylmethcathinone, 4-MMC), a psychostimulant drug that shows a strong resemblance to methamphetamine (METH). Unlike METH, which can produce clear long-term effects, the effects of 4-MMC have so far remained elusive. We employ manganese-enhanced magnetic resonance imaging (MEMRI), a highly sensitive method for detecting changes in neuronal activation, to investigate the effects of METH and 4-MMC on the brain.
  
  
  METHODS
  In Wistar rats we performed a MEMRI scan two weeks after binge treatments (twice daily for 4 consecutive days) of METH (5 mg/kg) or 4-MMC (30 mg/kg). Furthermore, locomotor activity measurements and novel object recognition tests were performed.
  
  
  RESULTS
  METH produced a widespread pattern of decreased bilateral activity in several regions, including the nucleus accumbens, caudate putamen, globus pallidus, thalamus, and hippocampus, as well as several other cortical and subcortical areas. Conversely, 4-MMC produced increased bilateral activity, anatomically limited to the hypothalamus and hippocampus. Drug treatments did not affect the development of locomotor sensitization or novel object recognition performance.
  
  
  CONCLUSIONS
  The pattern of decreased brain activity seen after METH corresponds closely to regions known to be affected by this drug and confirms the validity of MEMRI for detecting neuroadaptation two weeks after amphetamine binge treatment. 4-MMC, unlike METH, produced increased activity in a limited number of different brain regions. This highlights an important difference in the long-term effects of these drugs on neural function and shows precisely the anatomical localization of 4-MMC-induced neuroadaptation.
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland (Drs den Hollander, Dudek, Kankuri, Hyytiä, and Korpi); Hjelt Institute, Department of Forensic Medicine, Kytösuontie 11, FI-00014 University of Helsinki, Finland (Dr Ojanperä); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (Dr Korpi). denhollander.bjornar@gmail.com.
authors.forename: Bjørnar
authors.initials: B
authors.lastname: den Hollander
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland (Drs den Hollander, Dudek, Kankuri, Hyytiä, and Korpi); Hjelt Institute, Department of Forensic Medicine, Kytösuontie 11, FI-00014 University of Helsinki, Finland (Dr Ojanperä); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (Dr Korpi).
authors.forename: Mateusz
authors.initials: M
authors.lastname: Dudek
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland (Drs den Hollander, Dudek, Kankuri, Hyytiä, and Korpi); Hjelt Institute, Department of Forensic Medicine, Kytösuontie 11, FI-00014 University of Helsinki, Finland (Dr Ojanperä); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (Dr Korpi).
authors.forename: Ilkka
authors.initials: I
authors.lastname: Ojanperä
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland (Drs den Hollander, Dudek, Kankuri, Hyytiä, and Korpi); Hjelt Institute, Department of Forensic Medicine, Kytösuontie 11, FI-00014 University of Helsinki, Finland (Dr Ojanperä); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (Dr Korpi).
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland (Drs den Hollander, Dudek, Kankuri, Hyytiä, and Korpi); Hjelt Institute, Department of Forensic Medicine, Kytösuontie 11, FI-00014 University of Helsinki, Finland (Dr Ojanperä); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (Dr Korpi).
authors.forename: Petri
authors.initials: P
authors.lastname: Hyytiä
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland (Drs den Hollander, Dudek, Kankuri, Hyytiä, and Korpi); Hjelt Institute, Department of Forensic Medicine, Kytösuontie 11, FI-00014 University of Helsinki, Finland (Dr Ojanperä); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (Dr Korpi).
authors.forename: Esa R
authors.initials: ER
authors.lastname: Korpi
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods*; D058256:Brain Waves / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002712:Chlorides / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000008:administration & dosage*; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D011237:Predictive Value of Tests; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D002712:Chlorides; D017895:Manganese Compounds; D008694:Methamphetamine; C548233:mephedrone; C025340:manganese chloride
keywords: 4-methylmethcathinone; magnetic resonance imaging; mephedrone; methamphetamine; psychostimulants