title: Specific regions display altered grey matter volume in μ-opioid receptor knockout mice: MRI voxel-based morphometry.
abstract: OBJECTIVE
  μ Opioid receptor knockout (MOP-KO) mice display several behavioural differences from wild-type (WT) littermates including differential responses to nociceptive stimuli. Brain structural changes have been tied to behavioural alterations noted in transgenic mice with targeting of different genes. Hence, we assess the brain structure of MOP-KO mice.
  
  
  METHODS
  Magnetic resonance imaging (MRI) voxel-based morphometry (VBM) and histological methods were used to identify structural differences between extensively backcrossed MOP-KO mice and WT mice.
  
  
  RESULTS
  MOP-KO mice displayed robust increases in regional grey matter volume in olfactory bulb, several hypothalamic nuclei, periaqueductal grey (PAG) and several cerebellar areas, most confirmed by VBM analysis. The largest increases in grey matter volume were detected in the glomerular layer of the olfactory bulb, arcuate nucleus of hypothalamus, ventrolateral PAG (VLPAG) and cerebellar regions including paramedian and cerebellar lobules. Histological analyses confirm several of these results, with increased VLPAG cell numbers and increased thickness of the olfactory bulb granule cell layer and cerebellar molecular and granular cell layers.
  
  
  CONCLUSIONS
  MOP deletion causes previously undescribed structural changes in specific brain regions, but not in all regions with high MOP receptor densities (e.g. thalamus, nucleus accumbens) or that exhibit adult neurogenesis (e.g. hippocampus). Volume differences in hypothalamus and PAG may reflect behavioural changes including hyperalgesia. Although the precise relationship between volume change and MOP receptor deletion was not determined from this study alone, these findings suggest that levels of MOP receptor expression may influence a broader range of neural structure and function in humans than previously supposed.
  
  
  BACKGROUND
  This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
authors.affiliation: Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Kazumasu
authors.initials: K
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Sumiyoshi
authors.forename: Hiroi
authors.initials: H
authors.lastname: Nonaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kawashima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
mesh_terms: D000818:Animals; D066128:Gray Matter / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D017450:Receptors, Opioid, mu