title: Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a β-lactam antibiotic during cocaine withdrawal.
abstract: We report significantly decreased white matter protein levels in the nucleus accumbens in an adult mouse model of chronic cocaine abuse. Previous studies from human cocaine abuse patients show disruption of white matter and myelin loss, thus supporting our observations. Understanding the neuropathological mechanisms for white matter disruption in cocaine abuse patients is complicated by polydrug use and other comorbid factors, hindering the development of effective therapeutic strategies to ameliorate damage or compliment rehabilitation programs. In this context, our data further demonstrate that cocaine-induced loss of white matter proteins is absent in mice treated with the β-lactam antibiotic, ceftriaxone, during cocaine withdrawal. Other studies report that ceftriaxone, a glutamate transporter subtype-1 activator, is neuroprotective in murine models of multiple sclerosis, thereby demonstrating potential therapeutic properties for diseases with white matter loss. Cocaine-induced white matter abnormalities likely contribute to the cognitive, motor, and psychological deficits commonly afflicting cocaine abusers, yet the underlying mechanisms responsible for these changes remain unknown. Our observations describe an adult animal model for the study of cocaine-induced myelin loss for the first time, and highlight a potential pharmacological intervention to ameliorate cocaine-induced white matter loss.
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Kovalevich
authors.forename: Gladys
authors.initials: G
authors.lastname: Corley
authors.forename: William
authors.initials: W
authors.lastname: Yen
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
authors.forename: Dianne
authors.initials: D
authors.lastname: Langford
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D003042:Cocaine / Q000009:adverse effects*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism*; D047090:beta-Lactams / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D009419:Nerve Tissue Proteins; C493396:Slc1a2 protein, mouse; D047090:beta-Lactams; D002443:Ceftriaxone; D053148:Caspase 3; D003042:Cocaine