title: Microstructural changes to the brain of mice after methamphetamine exposure as identified with diffusion tensor imaging.
abstract: Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH-dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: McKenna
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA. Electronic address: gbrown@ucsd.edu.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Brown
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Archibald
authors.affiliation: Department of Radiology, School of Medicine, University of California, San Diego, 200 West Arbor Drive, M/C 0834, La Jolla, CA 92103, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Scadeng
authors.affiliation: Department of Radiology, School of Medicine, University of California, San Diego, 200 West Arbor Drive, M/C 0834, La Jolla, CA 92103, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bussell
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Kesby
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Virawudh
authors.initials: V
authors.lastname: Soontornniyomkij
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Achim
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
mesh_terms: D000818:Animals; D016880:Anisotropy; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D020772:Internal Capsule / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D013788:Thalamus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine
keywords: Diffusion tensor imaging; Fractional anisotropy; Magnetic resonance imaging; Mean diffusivity; Methamphetamine; Mouse