Chronic cocaine administration causes extensive white matter damage in brain: diffusion tensor imaging and immunohistochemistry studies

Psychiatry Res. 2014 Mar 30;221(3):220-30. doi: 10.1016/j.pscychresns.2014.01.005. Epub 2014 Jan 23.


The effect of chronic cocaine exposure on multiple white matter structures in rodent brain was examined using diffusion tensor imaging (DTI), locomotor behavior, and end point histology. The animals received either cocaine at a dose of 100mg/kg (N=19), or saline (N=17) for 28 days through an implanted osmotic minipump. The animals underwent serial DTI scans, locomotor assessment, and end point histology for determining the expressions of myelin basic protein (MBP), neurofilament-heavy protein (NF-H), proteolipid protein (PLP), Nogo-A, aquaporin-4 (AQP-4), and growth associated protein-43 (GAP-43). Differences in the DTI measures were observed in the splenium (scc) and genu (gcc) of the corpus callosum (cc), fimbria (fi), and the internal capsule (ic). A significant increase in the activity in the fine motor movements and a significant decrease in the number of rearing events were observed in the cocaine-treated animals. Reduced MBP and Nogo-A and increased GAP-43 expressions were most consistently observed in these structures. A decrease in the NF-H expression was observed in fi and ic. The reduced expression of Nogo-A and the increased expression of GAP-43 may suggest destabilization of axonal connectivity and increased neurite growth with aberrant connections. Increased GAP-43 suggests drug-induced plasticity or a possible repair mechanism response. The findings indicated that multiple white matter tracts are affected following chronic cocaine exposure.

Keywords: Cocaine; Diffusion tensor imaging; Immunohistochemistry; Magnetic resonance imaging; Neurobehavioral assay; Rodents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aquaporin 4 / metabolism
  • Axons
  • Behavior, Animal / drug effects*
  • Biomarkers / metabolism*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology*
  • Cocaine / administration & dosage
  • Cocaine / toxicity*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / pathology
  • Corpus Callosum / drug effects
  • Corpus Callosum / pathology
  • Diffusion Tensor Imaging*
  • Down-Regulation
  • GAP-43 Protein / metabolism
  • Humans
  • Immunohistochemistry
  • Internal Capsule / drug effects
  • Internal Capsule / pathology
  • Magnetic Resonance Imaging
  • Male
  • Myelin Basic Protein / metabolism
  • Myelin Proteins / metabolism
  • Myelin Proteolipid Protein / metabolism
  • Nerve Fibers, Myelinated / drug effects*
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology*
  • Neurofilament Proteins / metabolism
  • Neuronal Plasticity / drug effects
  • Nogo Proteins
  • Rats
  • Rats, Sprague-Dawley


  • Aqp4 protein, rat
  • Aquaporin 4
  • Biomarkers
  • GAP-43 Protein
  • Mbp protein, rat
  • Myelin Basic Protein
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Neurofilament Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, rat
  • Cocaine