Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data a...

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Autores principales:	Jhodie Rubina Duncan, Alec Lindsay Ward Dick, Gary Egan, Scott Kolbe, Maria Gavrilescu, David Wright, Dan Ian Lubman, Andrew John Lawrence
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bfa45bc4e552452096c95a099f491e69
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spelling	oai:doaj.org-article:bfa45bc4e552452096c95a099f491e692021-11-18T07:05:16ZAdolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.1932-620310.1371/journal.pone.0044790https://doaj.org/article/bfa45bc4e552452096c95a099f491e692012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028622/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T₂-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence.Jhodie Rubina DuncanAlec Lindsay Ward DickGary EganScott KolbeMaria GavrilescuDavid WrightDan Ian LubmanAndrew John LawrencePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44790 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jhodie Rubina Duncan Alec Lindsay Ward Dick Gary Egan Scott Kolbe Maria Gavrilescu David Wright Dan Ian Lubman Andrew John Lawrence Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
description	Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T₂-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence.
format	article
author	Jhodie Rubina Duncan Alec Lindsay Ward Dick Gary Egan Scott Kolbe Maria Gavrilescu David Wright Dan Ian Lubman Andrew John Lawrence
author_facet	Jhodie Rubina Duncan Alec Lindsay Ward Dick Gary Egan Scott Kolbe Maria Gavrilescu David Wright Dan Ian Lubman Andrew John Lawrence
author_sort	Jhodie Rubina Duncan
title	Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
title_short	Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
title_full	Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
title_fullStr	Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
title_full_unstemmed	Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
title_sort	adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/bfa45bc4e552452096c95a099f491e69
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Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.

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